WASHINGTON OPERATIONS
MTR-7152
CONTROLLED DISTRIBUTION
Environmental Assessment
of Atmospheric flitrosamines
P. WALKER
J. GORDON
L. THOMAS
R. OUELLETTE
FEBRUARY 1976
GiinnMi
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This report has been reviewed by the Strategies and Air Standards
Division of the United States Environmental Protection Agency, and
approved for publication. Approval does not signify that the contents
necessarily reflect the views and policies of the Environmental Protec-
tion Agency, nor does mention of trade names of commercial products
constitute endorsement or recommendation for use.
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CONTROLLED DISTR.
MITRE Technical Report
MTR-7152
Environmental Assessment
of Atmospheric flitrosamines
P. WALKER
J. GORDON
L. THOMAS
R. OUELLETTE
FEBRUARY 1976
CONTRACT SPONSOR U.S. Environmental Protection Agency
CONTRACT NO. 68-02 -1495
PROJECT NO. 077E
DEPT. W-54
THE
MITRE
McLEAAl, VIRGINIA 22101
This document was prepared for authorized distribution.
It has not been approved (or public release.
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Department Approval:,
-jUH
MITRE Project Approval;—^7^ /> ' / jCjlPl&.'ft' *
/
ii
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FORWARD
This report was prepared by The MITRE Corporation for the Office
of Air Quality Planning and Standards, U.S. Environmental Protection
Agency. The impetus for this document originated with the detection
of atmospheric nitrosamines in the vicinity of the FMC Corporation
facility in Baltimore, Maryland, and near the DuPont manufacturing
facility in Belle, West Virginia. As a result of these reports, it
was determined that the significance and impact of nitrosamines in
the atmosphere should be evaluated.
iii
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ACKNOWLEDGMENT
The authors wish to acknowledge those who gave generously of their
assistance and patience during the compilation of this document.
Those include Dr. George Singer, Oak Ridge National Laboratory; Dr.
Larry Keefer, National Cancer Institute; Dr. E. A. Walker, Inter-
national Agency for Research on Cancer; and Dr. David Fine, Thermo
Electron Corporation. Additional thanks are extended to John O'Connor,
Mike Jones, and John Bachmann of the United States Environmental Pro-
tection Agency, and to Barbara Fuller, Bob Strieter, and Len Benade
of The MITRE Corporation for the time and effort expended in comple-
tion of this study.
iv
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TABLE OF CONTENTS
Page
I. SUMMARY 1
A. CHEMICAL AND PHYSICAL PROPERTIES 1
B. TOXICOLOGY AND CARCINOGENICITY 2
C. MEASUREMENT TECHNOLOGY 3
D. AMBIENT DATA AND POPULATION AT RISK 3
E. SOURCES 5
F. CONTROL METHODOLOGY 8
G. CONCLUSIONS AND RECOMMENDATIONS 8
II. AIR POLLUTION ASSESSMENT REPORT 12
A. CHEMICAL AND PHYSICAL PROPERTIES 12
1. Properties and Chemical Reactions as a Class 12
2. Chemical Formation of Nitrosamines 19
B. TOXICOLOGY AND CARCINOGENICITY 32
1. General 32
2. Humans 41
3. Animals 42
C. MEASUREMENT TECHNOLOGY 43
1. Detection of Volatile Nitrosamines 47
a. Initial Separation from Product 47
b. Clean-up Procedures 48
c. Separation and Detection Techniques 50
2. Detection of Non-Volatile Nitrosamines 52
3. Detection of Atmospheric Nitrosamines 54
D. AMBIENT DATA AND POPULATION AT RISK 63
1. Ambient Nitrosamine Levels Reported 63
a. In Air 63
b. In Water 67
2. Resultant Exposed Population 68
E. SOURCES 72
1. Production and Use 72
2. Environmental Occurrence and Formation 88
a, Nitrosamines 88
b. NO 92
3. Formation as a Degradation Product of a More 99
Complex Compound
F. CONTROL METHODOLOGY 101
1. Nitrosamines 104
2. Precursors 106
III. CONCLUSIONS AND RECOMMENDATIONS 129
IV. REFERENCES 139
APPENDIX A AMINES MANUFACTURING AND DISPERSIVE USE A-l
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TABLE OF CONTENTS (CONTINUED)
LIST OF FIGURES
Figure Number Page
1 STRUCTURES OF VARIOUS NITROSAMINES 13
2 REACTIONS OF VARIOUS AMINES WITH 14
NITROUS ACID
3 PROPOSED MECHANISM FOR THE CONVERSION 16
OF TERTIARY AMINES TO NITROSAMINES
4 A HYPOTHETICAL NITROSATION OF A SUB- 21
STITUTED TRIBENZYLAMINE
5 SCHEME OF GC-TEA INTERFACE 60
6 BLOCK DIAGRAM OF DIMAZINE PROCESS 74
7 LOCATION OF AMINE PRODUCTION FACILITIES 78
8 SOME POSSIBLE ROUTES OF AMINES INTO 83
THE ENVIRONMENT
9 NATIONWIDE NO EMISSIONS TRENDS 1940-1972 98
x
10 SCHEMATICS FOR SYNTHESIS OF METHYLAMINES, 108
ETHANOLAMINES , AND MELAMINE
11 SCHEMATIC SYNTHESIS OF ALKYLAMINES 109
12 CONVENTIONAL COAL PROCESS COKING AND 114
COMBUSTION
13 REFINERY - CRUDE SEPARATION 115
14 REFINERY - PROCESSING OF LIGHT HYDRO- 116
CARBONS
15 REFINERY - PROCESSING OF INTERMEDIATE 117
HYDROCARBONS
16 REFINERY - PROCESSING OF HEAVY HYDROCARBONS 118
17 COAL GASIFICATION PROCESS MODULE 119
18 COAL LIQUEFACTION PROCESS MODULE 120
vi
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Table Number
II
III
IV
V
VI
VII
VIII
IX
XI
XII
XIII
XIV
XV
TABLE OF CONTENTS (CONTINUED)
LIST OF TABLES
DRUGS, PESTICIDES, AND NATURALLY
OCCURRING AMINES THAT HAVE EXPERI-
MENTALLY PRODUCED N-NITROSO COMPOUNDS
EITHER IN VIVO OR IN VITRO
RATE CONSTANTS FOR THE NITROSATION OF
FOUR AMINES
RATE CONSTANTS K AND K FOR AMINE
NITROSATION AT 25°C AND OPTIMUM pH
CONDITIONS FOR NITROSAMINE FORMATION
IN THE ATMOSPHERE
ACUTE TOXICITY OF SOME NITROSAMINE
COMPOUNDS
TUMOR SITES OF SOME NITROSAMINES
NITROSAMINES THAT HAVE BEEN TESTED AND
FOUND TO BE CARCINOGENIC
NITROSAMINES THAT DID NOT PRODUCE
TUMORS WHEN TESTED
RECOVERIES (1%) OF DIALKYL-, HETEROCYCLIC,
AND ALKARYL-N NITROSAMINES BY DISTIL-
LATION FROM NEUTRAL, ALKALINE, AND ACID
MEDIA
ANALYZED COMPOUNDS WHICH WERE FOUND TO
GIVE NO INTERFERENCE ON THE TEA
AMBIENT NITROSAMINE LEVELS DETECTED IN AIR
U.S. PRODUCERS OF AMINES
AMINE PRODUCTION FOR 1972
PROPERTIES OF REPRESENTATIVE AMINES
LOCATIONS OF SAMPLING AREAS AND CORRES-
PONDING LEVELS OF AMINES AND NO~ DETECTED
Page
23
28
30
33
37
38
44
45
49
62
65
76
79
86
89
vii
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Table Number
TABLE OF CONTENTS (CONTINUED)
LIST OF TABLES (CONCLUDED)
Page
XVI WORLDWIDE EMISSIONS OF NITROGEN 95
DIOXIDE IN 1967
XVII NATIONWIDE NO EMISSIONS, 1940-1970 97
x '
LIST OF FIGURES IN APPENDIX A
1 POSSIBLE ROUTES OF METHYLAMINE INTO A-2
THE ENVIRONMENT(1°)
2 POSSIBLE ROUTES OF DIMETHYLAMINE INTO A-3
THE ENVIRONMENT(2°)
3 POSSIBLE ROUTES OF TRIMETHYLAMINE INTO A-4
THE ENVIRONMENT(3°)
4 POSSIBLE ROUTES OF ETHYLAMINE INTO THE A-5
ENVIRONMENT (1°)
5 POSSIBLE ROUTES OF DIETHYLAMINE INTO THE A-6
ENVIRONMENT (2°)
6 POSSIBLE ROUTES OF TRIETHYLAMINE INTO A-7
THE ENVIRONMENT (3°)
7 POSSIBLE ROUTES OF METHYLDIETHYLAMINE A-8
INTO THE ENVIRONMENT (3°)
8 POSSIBLE ROUTES OF n-BUTYLAMINE INTO A-9
THE ENVIRONMENT (1°)
9 POSSIBLE ROUTES OF t-BUTYLAMINE INTO A-10
THE ENVIRONMENT (1°)
10 POSSIBLE ROUTES OF DI-n-BUTYLAMINE (2°) A-ll
11 POSSIBLE ROUTES OF 1,2 DIAMINOPROPANE A-12
INTO THE ENVIRONMENT (1°)
12 POSSIBLE ROUTES OF ALLYLAMINE INTO A-13
THE ENVIRONMENT (1°)
vlii
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TABLE OF CONTENTS (CONTINUED)
LIST OF FIGURES IN APPENDIX A (CONTINUED)
Figure Number Page
13 POSSIBLE ROUTES OF ETHANOLAMINE INTO A-14
THE ENVIRONMENT (1°)
14 POSSIBLE ROUTES OF DIETHANOLAMINE INTO A-15
THE ENVIRONMENT (2°)
15 POSSIBLE ROUTES OF TRIETHANOLAMINE INTO A-16
THE ENVIRONMENT (3°)
16 POSSIBLE ROUTES OF ME THY LE THANOLAMINE A-17
INTO THE ENVIRONMENT (2°)
17 POSSIBLE ROUTES OF ETHYLENEDIAMINE INTO A-18
THE ENVIRONMENT (1°)
18 POSSIBLE ROUTES OF HEXAMETHYLENEDIAMINE A-19
INTO THE ENVIRONMENT (1^
19 POSSIBLE ROUTES OF HEXAMETHYLENETETRAMINE A-20
INTO THE ENVIRONMENT (1°)
20 POSSIBLE ROUTES OF ETHYLENEIMINE INTO A-21
THE ENVIRONMENT (2°)
21 POSSIBLE ROUTES OF BENZYLAMINE INTO THE A-22
ENVIRONMENT (l°a)
22 POSSIBLE ROUTES OF ANILINE INTO THE A-23
ENVIRONMENT (l°a)
23 POSSIBLE ROUTES OF O-ETHYLANILINE INTO A-24
THE ENVIRONMENT (l°a)
24 POSSIBLE ROUTES OF O-DIAMINOBENZENE INTO A-25
THE ENVIRONMENT (l°a)
25 POSSIBLE ROUTES OF M-DIAMINOBENZENE INTO A-26
THE ENVIRONMENT (l°a)
26 POSSIBLE ROUTES OF P-DIAMINOBENZENE INTO A-27
THE ENVIRONMENTC l°a)
ix
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TABLE OF CONTENTS (CONCLUDED)
LIgT OF FIGURES IN APPENDIX A (CONCLUDED)
Figure Number Page
27 POSSIBLE ROUTES OF DIPHENYLAMINE A-28
INTO THE ENVIRONMENT (2°a)
28 POSSIBLE ROUTES OF P-AMINODIPHENYLAMINE A-29
INTO THE ENVIRONMENT (1°, 2°, a)
29 POSSIBLE ROUTES OF O-TOLIDINE INTO A-30
THE ENVIRONMENT Cl°a)
30 POSSIBLE ROUTES OF TOLUIDINES INTO THE A-31
ENVIRONMENT (l°a)
31 POSSIBLE ROUTES OF MELAMINE INTO THE A-32
ENVIRONMENT (l°a)
32 POSSIBLE ROUTES OF a & (3 -NAPHTHYLAMINE A-33
INTO THE ENVIRONMENT (l°pa)
33 POSSIBLE ROUTES OF BENZIDINE INTO THE A-34
ENVIRONMENT (l°a)
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I. SUMMARY
A. CHEMICAL AND PHYSICAL PROPERTIES
Nitrosamines, which are substances having an N-N=0 linkage, in-
clude a vast number of compounds. Since this nitroso group is the
only feature common to all, the physical and chemical properties of
the compounds extend over a wide range.
The formation of these compounds has been extensively investigated
in jLn vivo experiments and has recently been demonstrated during
atmospheric, or secondary, reactions. Measurement of in vivo forma-
tion rates has been attempted in order to establish reaction rates for
this method of amine nitrosation. During the experimental work it
has been established that numerous factors influence not only the
reaction rate but also the reaction yield. These factors include
simultaneous occurrence of nitrosation and resorption, amounts of
amine or nitrite present in the stomach, variations in acid secretion,
the action of catalysts and inhibitors, and the method of precursor
administration.
Although determination of the kinetics of the in vivo formation of
nitrosamines has not been definitive, the reaction rates for nitro-
samine formation in solution have been investigated with greater
success. The reaction kinetics may be pertinent to the formation of
nitrosamines in surface water with subsequent volatilization to the
atmosphere as well as to the nitrosation of atmospheric amines in the
particulate phase in the presence of water vapor. The nitrosation
rate for one amine, dimethylamine, has recently been established in
atmospheric experimentation.
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B. TOXICOLOGY AND CARCINOGENICITY
The reports of nitrosamine exposures, with subsequent effect, in
humans have been confined to two. A report of the accidental dimethyl-
nitrosamine poisoning of two men employed by an automotive production
facility where the compound was used as a solvent was published in
1956. One of the men recovered after exhibiting signs of liver damage.
The other died after an accident, and at necropsy a cirrhotic liver
with regenerating nodules was revealed. An additional report of the
hepatotoxicity of dimethylnitrosamine involved three men using the
nitrosamine for 10 months as a solvent in a British industrial research
laboratory. Two of the three men reported signs of liver injury, one
of which was confirmed as cirrhosis upon necropsy after death from
bronchial pneumonia. The other technician who had experienced a hard
liver with an irregular surface, recovered after termination of exposure.
The vast majority of the direct biological evidence reported for
the carcinogenicity of nitrosamines has been gathered using laboratory
animals. The evidence of carcinogenicity in man is only indirect.
Studies have shown nitrosamines to be versatile in their induction of
organ tumors with practically all locations reported as the target of
at least one compound. The versatility of action is enhanced by the
many different species, including subhuman primates that have been
experimentally affected by the carcinogenic properties of nitrosamines.
One compound, diethylnitrosamine has exhibited an effect in rat, mouse,
hamster, guinea pig, pig, rabbit, dog, rainbow trout, aquarium fish,
grass parakeet, and monkey. Oral administration is an effective
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method of dosage, with small daily doses over an extended period being
more effective than large single doses. To date, no animal species
has shown resistance to the carcinogenic action of the most potent
N-nitroso compounds, which leads to the real possibility that man would
also be affected.
C. MEASUREMENT TECHNOLOGY
Until recently, detection of nitrosamines at the low environmental
concentrations expected has been difficult. This difficulty arises
from some of the general properties of these compounds: (1) they do
not have well-defined absorption spectra, and (2) they are difficult
to separate from other analysis-interfering compounds (nitrogen-con-
taining compounds).
Many techniques have been utilized in the past for detection of
nitrosamines. However, some of these techniques (i.e., colorimetry,
ultra-violet spectrophotometry) are not sensitive enough to detect
low concentrations. The gas chromatography/thermal energy analyzer
(GC/TEA) and the gas chromatography/high resolution mass spectrometry
techniques now available appear to be the most sensitive techniques.
D. AMBIENT DATA AND POPULATION AT RISK
A recent report of dimethylnitrosamine levels of 0.033 to 0.96
¦j 3
vtg/m in Baltimore, Maryland, and 0.014 to 0.051 (Ag/m in Belle, West
Virginia was the first documentation of atmospheric nitrosamines.
Nitrosamines were not detected at the other sampling sites (Wilmington,
Delaware; Philadelphia, Pennsylvania; Waltham, Massachussets).
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This report generated much debate over the analytical technique used,
which was the GC/TEA.
The original findings were confirmed by repeated sampling of
Baltimore air and subsequent detection of nitrosamines. They were
also detected independently by a second researcher in samples that
were collected on the same days and analyzed by a different technique.
The nitrosamine levels reported by the two investigators were essen-
tially the same.
The workers in any plants where nitrosamines are manufactured,
used, or generated are at risk of exposure. In addition to industry,
this would include workers in laboratories where samples are analyzed
for nitrosamines, animal attendants and other workers in laboratories
where experiments involving nitrosamines are being conducted, and also
workers in laboratories where tobacco smoke is generated or the
general population which is exposed to tobacco smoke. Exposure of the
general population to industrial emissions or food and water that con-
tain nitrosamines may also add to the body burden. It is probable that
rocket launch pads are the site of high concentrations of nitrosamines
during and after rocket launches and any personnel present at such
times would also be exposed. The general population may also run the
risk of exposure to atmospheric nitrosamines formed by secondary pro-
cesses; this may occur in areas where there are high concentrations of
both amines and NO gases.
x
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The effects of this exposure are difficult to assess due to the
lack of sufficient data pertaining to inhalation of low levels of
nitrosamines. Studies that have been conducted have illustrated that
nitrosamines can .induce tumors in many body tissues. Of the approxi-
mately 100 N-nitroso compounds studied, more than 80 have been shown
to be carcinogenic in test animals. Some of these have produced car-
cinogenic effects after administration of a single dose. Extrapolation
of these data for humans, although not conclusive, indicates that a
possible risk may exist as a result of atmospheric nitrosamines.
E. SOURCES
Synthetic production of these compounds occurs but is limited to
very small quantities. The only nitrosamine produced in significant
amounts is N-nitrosodiphenylamine, a non-carcinogenic compound, which
is used as a retardant in the production of rubber. Several other
nitrosamines are produced in kilogram quantities primarily for sale to
the scientific community for use in research.
Nitrosamines have been patented for use, but they are not cur-
rently used, as gasoline and lubricant additives, pesticides, and
antioxidants. They have also been used, but are no longer, as
fungicides, nematocides, inhibitors of soil nitrofication, plasti-
cizers, acrylonitrile polymers, synthetic Intermediates, and
industrial solvents in the plastic and fiber industries. Two com-
pounds, di-n-butyl-nitrosamine and dimethylnitrosamine , can be used
as intermediates in the production of their respective hydrazines.
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Nitrosamines have formerly been used in condensers to increase the
dielectric constant and as softeners for copolymers.
The environmental occurrence of nitrosamines has been documented
in a wide variety of substrates. The wheat plant, wheat grain, un-
processed milk and cheese, tobacco, tobacco smoke, fish meal, smoked
meats, and alcoholic beverages have been found to contain nitroso
compounds. The exact origin of the nitrosamines is not clear.
* V *
One widely recognized explanation for the environmental appearance
of nitrosamines is synthesis, either in vivo or through secondary
reactions. Secondary amines are known to react with nitrites to form
nitrosamines under conditions of defined pH and other conditions similar
to those in the mammalian stomach (in vivo formation). Recently, it
was determined that at least one amine, dimethylamine, will nitrosate
in an atmosphere containing water vapor, NO, and nitrous acid.
An upper limit rate constant, calculated for the bimolecular reaction,
indicated that secondary formation in urban, polluted atmospheres would
be theoretically feasible. However, the current evidenfce indicates
»
this theoretical formation would only occur during darkness.
The widespread availability of nitrosamine precursors enhances
the possibility of in vivo or secondary formation. Nitrates and
nitrites are used as food additives for color fixation, preservation,
and flavor enhancement and could be used as precursors for in vivo
formation. The pool of atmospheric N0x is contributed to by two com-
monly occurring natural processes, bacterial degradation and slow
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reactions of fossil fuels, as well as by an anthropogenic pollution
source, fuel combustion processes. Background atmospheric concentra-
tions of NO and NO^ detected in the United States are 2 ppb and 4 ppb,
respectively. These atmospheric NO gases are available for secondary
nitrosamine formation.
Amines are also readily available for utilization during de novo
or secondary formation. They are found in fish products, cereals,
tobacco, dyes, drugs, pesticides, and many other organic materials,
and in this state would be available for in vivo synthesis. Forma-
tion of amines has been indicated during food cooking processes as well
as through commercial synthesis. Amines are also emitted from coking
plants, sewage treatment facilities, and during organic decomposition
(e.g., feedlots). Emissions are also suspected to emanate from solid
waste disposal systems. Another source of amines to the environment
is due to the disposal or use of manufactured products containing
amines. These amine sources would be available for secondary synthe-
sis . Amines are not routinely monitored in the atmosphere since de-
fined health standards have not been established. However, they have
been detected and quantitated in water and values of 0.1 to 20 (Jg/kg
were reported.
The degradation of a more complex compound nay also contribute
to the environmental load of nitrosamines. Nltrilotriacetic acid (NTA)
has been shown by some investigators to degrade into amines which are
nitrosated. However, rapid degradation which would not allow sufficient
time for nitrosation of the amines has been reported to occur. The
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degradation of hydrazine may be another possible candidate for nitro-
samine formation.
F. CONTROL METHODOLOGY
Control methodology for nitrosamines is approached from two direc-
tions, i.e., control of the compound as it is emitted from chemical
processing, or control of the precursors.
Good housekeeping practices (e.g., limitation of spills, prompt
location and correction of leaks) and use of closed systems wherever
possible will minimize worker exposure to nitrosamines as well as
nitrosamine emissions from a plant. Wet scrubbing followed by proper
incineration techniques can effectively limit nitrosamine emissions
from the plant to the atmosphere.
Amine emissions can be controlled using different techniques de-
pendent on the source of the emission. Variations in methodology em-
ployed vary in the following situations: manufacture, industrial use,
refining, incineration, combustion, and sewage treatment. Limited
controls for NO^ and other nitrogenous compounds are possible, however,
because these controls are not absolute, and they will probably not
have as great an impact as will the control of amines. Although limited
controls are presently available, there is still an ongoing research
effort to develop catalysts for the control of NO emissions from the
automobile;
G. CONCLUSIONS AND RECOMMENDATIONS
The following specific conclusions can be drawn concerning the
»
chemical activity and reactivity of nitrosamines.
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• Based on the chemistry of nitrosamine formation and the kinetics
of amine nitrosation, only secondary amines and a few tertiary amines
(of high volatility) readily react with nitrous acid to form nitro-
samines. Therefore, only emissions of these amines could be of conse-
quence during secondary formation.
• Gaseous nitrosamines are characteristically photosensitive
and can be denitrosated to their precursors by both visible and ultra-
violet light. Therefore, secondary synthesis may be a cyclic process.
However, because of their photolability, nitrosamine buildup in the
atmosphere is not likely.
• There exist metallic catalysts that may facilitate nitrosamine
formation under conditions that would ordinarily not have induced
nitrosation. As a result, nitrosamine formation may occur in atmos-
pheres containing lower contaminant concentrations than expected.
However, this action is not completely documented and is speculative
at this time.
• The kinetics of amine nitrosation in solution follow a dinitro-
gen trioxide mechanism and these reactions may have a bearing on the
atmospheric burden as the compounds may volatilize from the water or
soil into the ambient air. Also, these reactions may occur in.water
droplets or particulate matter in ambient atmospheres,
• The versatility and potency of nitrosamines administered to
animals indicates that, although only liver damage has been documented
in humans, carcinogenic hazards may be incurred by humans exposed to
nitrosamines .
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• Artifact formation in cold traps, initially thought to be a
significant problem increasing the nitrosamine content of an air sample,
only accounts for a very small quantity of nitrosamine formation. As
a result, the nitrosamine concentrations detected and reported are
probably accurate.
• Individuals residing or working in areas of amine emissions
and high NO concentrations may be risking exposure to nitrosamines,
as it has been established that under certain conditions, amines may
nitrosate in polluted urban atmospheres. Individuals exposed to
direct emissions of nitrosamines may be incurring a higher degree of
risk. Exposure may also occur during consumption of certain foods or
combinations of foods as well as through water.
Considering the potential hazards indicated by the experimental
nitrosamine research and the recent confirmation of atmospheric nitro-
samine detection, further research is indicated. It is apparent that
several areas of action, if pursued, will enlarge the knowledge base
as well as denote an appropriate pathway for resolution of the problem.
These areas include:
1. Evaluation of the nitrosamine sampling and identification
techniques presently available.
2. Institution of inhalation studies to document the health
effects which may be associated with the low levels of nitro-
samines detected in ambient air.
3. Determination of the principal source(s) of atmospheric
nitrosamines.
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Expansion of the monitoring network to include all the sus-
pected areas of nitrosamine occurrence.
Investigation of the chemical properties associated with
nitrosamines in relation to the kinetics of formation (e.g.,
codistillation and evaporation from aqueous surfaces , par-
ticulate reactivity, stability under expected environmental
conditions).
Development of control technology for amine emissions.
Investigation of substitutes for nitrates/nitrites.
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II. AIR POLLUTION ASSESSMENT REPORT
A. CHEMICAL AND PHYSICAL PROPERTIES
1. Properties and Chemical Reactions as a Class
N-nitrosamines are compounds having the general structure
R
,~>N
¦N=0
R'
where R and R' may be alkyl or aryl groups or may represent carbon
atoms in a ring structure (see Figure 1). Thus, the nitrosamine may
be dialkyl, diaryl, alkaryl, or cyclic (1). They are most commonly
prepared by the reaction of secondary amines with nitrous acid (2):
Primary and tertiary amines behave somewhat differently when treated
with nitrous acid. Primary aliphatic amines react to yield nitrogen
and alcohols, while tertiary aliphatic amines usually form unstable
salts which are destroyed on neutralization (3), Primary aromatic
amines form diazonium salts (one of the most important reactions in
organic chemistry) , (4) and tertiary aromatic amines undergo ring sub-
stitution with a nitroso group joined to a carbon atom generally in
the para-position (3) (see Figure 2) . All these reactions, despite the
differences in final product, involve the same initial step, i.e., an
electrophilic attack by the nitrosonium ion (+N0) and consequential dis-
placement of a hydrogen ion, occurring at the position of highest electron
R'
R
N—H + HO—N=0
N—N=0 + H20
12
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CH„
CH„
. CH„
. CH„
:N - N=0
N
N ==0
NITROSOPIPERIDINE
NITROSOPYRROLIDINE
N=0
NITROSOMORPHOLINE
— COOH
NITROSOPROLINE
ch 2»ch-ch2-n-ch2-ch2-ch»ch2
N ¦ -0
V-BUTENYL ((3-PROPENYL) NITROSAMINE
CH-
,CH2 - COOH
'N
N
NITROSOSARCOSINE
'N
COOH
NITROSOPIPECOLIC ACID
FIGURE 1
STRUCTURES OF VARIOUS NITROS AMINES
13
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(1) primary aliphatic amine and nitrous acid ~nitrogen + alcohol
/H
R N<^ + HO-N+O N2 + R-OH + ^0
H
(2) tertiary aliphatic amine + nitrous acid «-salt
R
R - N - R + H0-N=0 -NR3H(+) + NO^"^
|nr3h(+)no2(-:)J
(3) primary aromatic amine + nitrous acid ^diazonium salt
<^)-m2 + H0-N-0, + Cl^
NaN02 + HC1
(4) tertiary amine + nitrous acid ^p-nitroso compound
R
<0^ N + H0-N=0 »-0=N
FIGURE 2
REACTIONS OF VARIOUS AMINES WITH NITROUS ACID
14
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availability in primary and secondary amines (the amino nitrogen) (5).
Tertiary aromatic amines, which have no hydrogen or nitrogen, are
attacked instead at the highly reactive ring. Some tertiary aliphatic
and aromatic amines (particularly those aromatics with the para-position
blocked) react with nitrous acid to yield an N-nitroso derivative of a
secondary amine, with the group lost from nitrogen appearing as an aldehyde
or ketone. This latter reaction has not been fully elucidated, but
seems also to involve the initial attack of nitrogen by the nitrosonium
ion (5). Smith and Loeppky (6) have suggested a mechanism, which appears
in Figure 3.
Since the nitroso group is the only feature common to all, the
physical properties (e.g., solubilities and volatilities) of nitro-
samines extend over a wide range. Many are oily yellow or orange-
yellow liquids or even solids at room temperature. They are often
sparingly soluble in water, but soluble in many organic solvents (1,2).
The low molecular weight nitrosamines are volatile compounds (i.e.,
nitrosodimethyl-, nitrosomethyl-, nitrosobutyl-, and nitrosomethyl-
vinylamine), while almost all nitrosodialkylamines are steam volatile (7).
Nitrosamines may be considered to have structures comparable to
esters or to acetyl derivatives of amines. Like these compounds,
nitrosamines are hydrolyzed by boiling dilute hydrochloric acid with
recovery of the original amine by alkali neutralization and steam
distillation (3) . The nitroso group has the same effect as an acetyl
substituent (neutralization of the basic character of nitrogen), and
15
-------
HNO CHR
r N CHR R„N^ > RJi=CR + HNO
2 1 NO
h2o
HNO,
R2N NO <-
r2n h2 + r2c=o
CTn
FIGURE 3
PROPOSED MECHANISM FOR THE CONVERSION
OF TERTIARY AMINES TO NITROSAMINES
-------
thus, like the acetyl derivatives, the nitrosamines are neutral sub-
stances . This neutrality and the differing behavior of the three types
of amines to nitrous acid have been used as a separation method (3).
When nitrous acid reacts with a mixture of the three types of amines,
the primary amino component is converted to alcohols, the secondary
amines form neutral nitrosamines, and the tertiary amines can be
separated by extraction of an ether solution with mineral acid. The
unextracted neutral material may then be acid-hydrolyzed, regenerating
the secondary amines from the nitroso derivatives. The free base is
then liberated with alkali.
Nitrosamines may also be prepared by the reduction of nitramines
(4):
R. chemical or R.
^>N W)- + 2H/ electrolytic ~
R' 1 R'
or, less commonly, by the methylation of a sodium diaryl aryldiazoate
(4):
All
Ar - N=«*=N-0-Na + CH.I > ^>N - N-0 + Nal
h3c
The gaseous nitrosamines are characteristically photosensitive,
demonstrating marked sensitivity to ultraviolet light (\max - 200 nm)
which splits off the nitrosyl group. They may also be de-nitrosated
by visible light. The absorption peaks of nitrosamines in water are
at ultraviolet 230 to 240 nm (Sabout 10,000) and 330 to 350 nm (2 about
100) (1,7,8). The rate of this denitrosation varies from compound to
17
-------
compound and has not yet been quantitated except for dimethyl nitro-
samine (see Section II .E.2., Environmental Occurrence).
The nitroso group is stable to strong alkali, but hydrolysis
with reversion to the secondary amine occurs on prolonged heating in
acid conditions (1,4,7):
The N-nitroso group may also be removed by treatment with urea, the
products in the case of m-nitro-N-nitroso-Nnnethylaniline being nitric
oxide, nitrogen, carbon dioxide, hydrogen, and m-nitro-N-methylaniline
The dialkylnitrosamines are generally more stable in acid solutions
than the diarylnitrosamines. The alkaryl nitrosamines, however, re-
arrange in concentrated acid solutions to yield C-nitroso compounds
(9). When, for example, concentrated hydrochloric acid is added to a
solution of N-nitroso-N-methylaniline in alcohol at room temperature,
the substance rearranges to form p-nitroso-N-methylaniline, which may
be separated as the crystalline hydrochloride (3).
(methylphenylnitrosamine)
A reaction of preparative value consists of the reduction of nitro-
samines to substitued hydrazines (1,3,4). This synthesis is best
18
¦N===0 + H20/(HC1) >
HONO
(4).
1. HCl, alcohol-ether, 25%
N - N 0 2. Na~CO„
N-nitroso-N-methylaniline
p-nitroso-N-methylaniline
-------
performed using either zinc and dilute acetic acid or sodium amalgam
as reducing agents. Once again, using N-nitroso-N-methylaniline for
illustration:
C H C H
6 5^>N - B_0 W(Znf£S 2°"80^ 6 5>N " ^
ch3 ' ch3
oi-me thy lphenylhydraz ine
Reduction with more powerful reagents like tin or zinc and a mineral
acid (or and platinum on barium sulfate) results in the splitting
of the N-N bond and formation of the secondary amine (3,4):
C6H5 N(CH3)N0 + 6H/(Sn/HCl,aq.) —> - NH - CH3 + NH3 + H20
N-nitroso-N-methylaniline N-methylaniline
(c6h5)2n - no + h2 Pt on BaSQ4 ^ (c6h5)2nh + n2 + h2o
N-nitrosodiphenylamine diphenylamine
Oxidation of nitrosamines by trifluoroacetic acid/50% H202 or by
trifluoroperacetic acid yields the corresponding nitramines (7,10,11).
H„0_ m Mn
>M°2
R' R'
2. Chemical Formation of Nitrosamines
The formation of nitrosamines from amines and various en-
vironmental nitrogen sources has been investigated. Several theories
hypothesizing the role of metallic compounds in these environmental
nitrosation reactions have been proposed. These theories are primarily
speculative and should be investigated further. One of these involves
the catalytic action of these metals, which has been indicated during
19
-------
formation of N-nitroso compounds (15). The template activity of a
metal has been illustrated, facilitating a reaction that would not
have otherwise occurred (12). Another metallic property valuable in
effecting N-nitrosation at alkaline pH is the surperacid effect created
by certain iron species (13-15). An additional action of metallic
ions during the process of nitrosation may be the enhanced capacity for
reduction-oxidation effected by the metals' presence. This property
may greatly enlarge the number of potential precursors of environmental
nitrosamines. As an example, the lower oxidation states of nitrogen,
after oxidation by metallic ions, may be capable of nitrosation. If
this activity proves to be significant, an expansion of the list of
possible nitrosamine precursors will occur.
Factually, several pathways for the chemical formation of nitro-
samines are known. Nitrosation of tertiary amines and N',N'-dialkyl-
hydrazides can, with moderate difficulty, produce nitrosamines (16).
The nitrosation of substituted tribenzylamines probably yields a se-
condary amine after the first nitrosation and a nitrosamine after the
second, (17) as illustrated in Figure 4.
Nitrosation of trialkylureas yield NO-ureas with small amounts of
dialkylnitrosamines produced also. The following ureas also produced
dialkylnitrosamines after nitrosation: 1,1-dialkylureas, 1,1-diakyl-
3-phenylureas, 1,1-dialkylthioureas, and tetra-alkylureas. The nitro-
sation of dimethylformamide can even produce small amounts of dimethyl-
nitrosamine (18,19,20).
20
-------
\
R1
N2°3
^ - CH2 - R"— >
/I
CH„ - R"
NO
R
R'
\
/
N=CH-R"
+ h2o
J-NO <
N2°3
V
wH + R"
/
CHO
R'
FIGURE 4
A HYPOTHETICAL NITROSATION OF A SUBSTITUTED TRIBENZYLAMINE
-------
N-alkylureas, -asylureas, -alkylcarbamates, secondary aromatic
amines, secondary amine derivatives of piperazine and morpholine, and
tertiary amines are more readily nitrosated than simple aliphatic
secondary and tertiary amines, N-acylureas, and N-alkylguanidines.
Therefore, the former are of greater interest as potential precursors
for in vivo formation of nitrosamines. The kinetics of in vivo nitro-
samine formation can be modified by catalysts (e.g., thiocyanate and
formaldehyde) particularly for amines when the nitrite concentration
is low and the mechanism (nitrosating agent) is suppressed (20).
Nitrate is generally first converted to nitrous acid, which is
then converted to an active nitrosating agent, e.g., nitrosyl thio-
cyanate (ON-NCS), nitrosyl halide (NOX), nitrous anhydride (N^), or
nitrous acidium ion (H^N0^). The kinetics of nitrosation of many
compounds have been extensively studied and a review of the experi-
mental work follows (20).
Nitrosation of secondary amines may be important since their
occurrence in food, particularly after fermentation in cooking, has
been reported (21) . Secondary amines are also present in drugs and
pesticides. Table I lists a variety of amines, generally available
to organisms which occur naturally, or as drugs and pesticides, that
have produced nitrosamines under experimental conditions.
Nitrosation of primary amines most likely results in the brief,
intermediate formation of a nitrosamine which rapidly changes to a
22
-------
TABLE I
DRUGS, PESTICIDES, AND NATURALLY OCCURRING AMINES THAT HAVE
EXPERIMENTALLY PRODUCED N-NITROSO COMPOUNDS EITHER IN VIVO OR IN VITRO
Compound
*
Class
Product
References
Secondary amines
AA
Morpholine
D»P
NO-derivative
8
Piperazine
D
MNP,DNP
8
Atrazln
P
NO-derivative
28
Simazin
P
NO-derivative
28
Phenmetrazine
D
NO-derivative
30
Ethambutol
D
NO-derivative
31
Ziram
P
DMN
28
Thiram
P
DMN
41
Ferbam
P
DMN
41
Tertiary amines
Aminopyrine
D
DMN
27,32
Oxytetracycline
D
DMN
27,32
Chlorpromazine
D
DMN
32
Dextropropoxyphene
D
DMN
32
Chlorpheniramine
D
DMN
32
Methadone
D
DMN
32
Methapyrilene
D
DMN
32
Quinacrine
D
DEN
32
Lucanthone
D
DEN
32
Tolazamide
D
NO-hexamethyleneimine
27,32
Cyclizine
D
DNP
32
Trimethylamine
N
dmn
29,23,33,34,35
2-Dimethylaminoethanol
N
DMN
33
N,N-Dimethylglycine methyl ester
-
DMN
33
N,N-Dime thylglycine
N
DMN,NO-sarcosine
36
Tr iethanolamine
NO-die thanolamine
23
-------
TABLE I (Concluded)
Compound
*
Class
Product
References
Tertiary amines (cont'd)
Nitrilotriacetic acid
-
NO-iminodiacetic acid
23
N,N-Dimethyldodecylamine
-
DMN,NO-N-methyldodecyl-
23
amine
Nicotine
N
NO-nornicotine
37
Pyribenzamine
D
NO-derivative
38
Carbaryl
P
NO-carbaryl
28
Propoxur
P
NO-propoxur
28
Benzthiazuron
P
NO-benzthiazuron
28
Quaternary amines
Tetramethylammonium chloride
-
DMN
33
Neurine chloride
N
DMN
33
Acetylcholine
N
DMN
33
Choline
N
DMN
33
Betaine
N
dmn
33
Carnitine
N
DMN
33
Trimethylamine-N-oxide
N
DMN
23,35
Trlbenzylamine-N-oxide
Dibenzylnitrosamine
22
*
D - drug
P - pesticide
N - naturally occurring
NO - derivative of the compound nitrosated
Adapted from S. S. Mirvish, "Formation of N-Nitroso Compounds: Chemistry, Kinetics, and in
vivo Occurrence," Tox. & Appl. Pharma., 31, 1975.
-------
diazo compound as follows:
NOX + RNH2 FaSt> rSh2NO FaSt> RNNOH
Therefore, it is probable that these compounds are not of great signi-
ficance to the jji vivo formation of stable nitrosamines (20).
In vivo nitrosation of simple tertiary amines will probably prove
to be an insignificant factor in the formation of nitrosamines, based
on the nitrosation kinetics of these compounds and on the lack of
experimental tumor induction reported using nitrite and trimethylamine
(20,22); however, this does not eliminate the possibility of ambient
de novo formation from these compounds.
Measurement of the in vivo formation of nitrosamines has been
attempted in order to establish reaction rates for the Jin vivo nitro-
sation of amines. It has been clearly demonstrated that numerous
factors influence not only the reaction rate but also the reaction
yield.
Sander et _al. found that the first complication evolved due to
the simultaneous occurrence of nitrosation and resorption of the
nitrosamine In vivo. Because the resorption is rapid, the nitrosamine
detected and measured in the stomach represents only a fraction of
the synthesis. An additional difficulty reported in establishing
reaction rates was attributed to differences in amine or nitrite pre-
sent in the stomach, variations in acid secretion of the animals, and
presence or absence of possible catalysts and inhibitors. One further
determining factor is the method of administration of the precursors.
25
-------
Gastric intubation results in high concentrations of the nitrosamine
in only a part of the stomach, while premixing of the components with
the feed results in homogenous distribution throughout the stomach (42).
Although the kinetics of iji vivo formation of nitrosamines have
not been definitively established, the reaction rates for formation in
solution have been investigated with greater success. Since amines
can be expected to be present in the atmospheric environment adsorbed
on particles or solubilized in water droplets, the laboratory solution
chemistry of these materials may well be relevant to the kinetics of
nitrosamine formation in ambient air.
The kinetics of dimethylamine nitrosation in solution follow the
dinitrogen trioxide mechanism as represented in the following equations:
rate - ^ x [RjNH] x [HNO^2 (A)
2
rate = x [total amine] x [total nitrite] (B)
Equation A is calculated using the concentration of nonionized amine
and free nitrous acid. Because both of these concentrations will
fluctuate with pH, is independent of pH. Equation B is calculated
using the total concentration of dimethylamine and nitrite; therefore,
K2 is dependent upon pH. This reaction rate for dimethylamine
exhibits a maximum value at pH 3.4, close to the pK of 3.37 for
cl
nitrous acid (43).
For equation A, the nitrosating agent is not free nitrous acid,
but dinitrogen trioxide (N2°3^» which forms rapidly and attacks the
26
-------
unprotonated amine as follows:
2HN02 £=— N203 + H20
slow + ^ —
R2NH + N203 R2N^ r + N02
NO
In the presence of a halide anion (X ), a covalent nitrosyl
halide can be formed, which is then the nitrosating agent.
—* faof
HN02 + H30 + X ^ NOX + 2H20
For this catalyzed nitrosation, a different kinetic equation has been
found applicable (44)s
rate = x [HN02] x [R^O*] x [X ] x [R^NH] (C)
The nitrosation rate constants of four amines, using ultraviolet
absorption of the nitrosamines to quantify the reaction, are contained
in Table II. The reactions followed equations A and B at the optimum
pH. The relative reaction rates under standard conditions, repre-
sented by K2> increased 185,000 fold in progression from piperidine
to piperazine, while K^, representing the reaction of the nonionized
species of these amines, fluctuated only fourfold. Examination of
the pK values of the various amines reveals that the less basic an
a
amine is, the more readily it is nitrosated. The primary nitrosation
difference among the amines is, therefore, due to the proportion of
reactive nonionized amine at optimum pH and this, in turn, depends
on the basicity of the amine (45).
27
-------
TABLE II
RATE CONSTANTS FOR THE NITROSATION OF FOUR AMINES
AMINE
PKa
OPTIMUM
pH
*
K2
*
Kx x 10~6
Piperidine
11.2
3.0
0.027
8.6
Dimethylamine
10.72
3.A
0.10
8.9
Morpholine
8.7
3.0
14.8
15.0
Piperazine
5.57
3.0
5000.0
3.7
< -2 2-1
Values at the optimum pH in moles 1 minute
Source: Adapted fromMirvish, S. S., 1972. "Kinetics of N-nitrosation
reactions in relation to tumorigenesis experiments with
nitrite plus amines or ureas." N-Nitroso Compounds Analvsis
and Formation, 104-108.
28
-------
In a subsequent publication, the rate constants and ^ were
established for 15 amines (see Table III) . As previously elucidated,
the ease of nitrosation, as given by K0, increase as the pK , or
i, 3
basicity, decreases. The nitrosations all were found in accordance
with equations A and B, except for aminopyrine, N-methylaniline, and
the three amino acids. These variations were attributed to increased
complexity of kinetics because protonation of the carboxy group
affects basicity of the amino group (20).
The atmospheric chemistry of secondary nitrosamine formation has,
until recently, not been elucidated. However, the formation and de-
gradation rates for dimethylnitrosamine have recently been discerned
¦k
(46). Dimethylamine and nitrous acid, both in the gaseous state, have
been shown to react, yielding nitrosodimethylamine. One ppm di-
methylamine reacted with 0.5 ppm nitrous acid vapor in equilibrium
with 2 ppm NO, 2 ppm N02, and 13,000 ppm 1^0 in air, revealed a reaction
rate for the amine of 4 percent per minute with dimethylnitrosamine
iff
To determine the nitrous acid concentration in the air, the following
equation can be utilized:
P(HN02)^/pN0 x pN02 x pH20 - 1.5 x 10~6 reciprocal ppm
p - partial pressure
This can then be inserted for the nitrous acid value in the equili-
brium reaction.
29
-------
TABLE III
RATE CONSTANTS AND FOR AMINE NITROSATION AT
25°C AND OPTIMUM pH
K9
Ki
AMINE
PKa
OPTIMUM
PH
I
,„-2 -1.
(M sec )
1
/„-2 -1.
(M sec )
* **
Piperidine
11.2
3.0
0.00045
1.4
ick
Dimethylamine
* **
Pyrrolidine
10.72
11.27
3.4
3.0
0.0017
0.0053
1.5
21.0
N-Methylethanolamine
9.5
3.2
0.010
0.62
•k
N-Methylbenzylamine
**
Proline
9.54
3.0
0.013
0.92
***
2.5
0.037
1.4
**
Sarcosine
***
2.5
0.23
2.6
Prolylglycine
**
Hydroxyproline
8.97
3.0
0.25
5.0
***
2.5
0.31
2.1
Prolylleucylglycineamide
8.97
3.4
0.38
6.2
Morpholine
8.7
3.4
0.42
2.3
Mononitrosopiperazine
****
Aminopyrine
6.8
5.04
3.0
2.0
6.7
80.0
0.83
1.0
*
Piperazine
5.57
9 .8
3.0
3.0
83.0
83.0
0.62
0.62
N-Methylaniline
4.85
*****
250.0
18.0
Examined in 50mM citrate-perchlorate buffer which may have shifted
the pH maximum from 3.4 to 3.0, but did not appreciably affect and
K„ at optimum pH.
ft*
Naturally occurring.
No pK is given because of the complex ionization.
**** ^
Examined at 0°C.
Calculated from rates at pHl.
Source: Adapted from Mirvish, S. S., 1975. "Formation of N-Nitroso
Compounds: Chemistry, Kinetics, and in vivo Occurrence."
Toxicology and Applied Pharmacology, 31, 325-351.
30
-------
as the major product. Dimethylamine, at a concentration of 1 ppm
reacted with 1 ppm NC^ and 4 ppm NO in dry nitrogen, is only nitro-
sated at a rate of 1 percent per minute. Calculation of the upper
limit rate for both reactions facilitated the determination that the
nitrous acid molecule is the principal nitrosating agent. An upper
limit rate constant, k « 0.1 ppm \ min. \ was calculated for this
bimolecular reaction, indicating that formation in ambient atmospheres
would be feasible. Additional degradation studies performed at this
time indicated that the compound half-life, as a result of photolysis
during normal atmospheric conditions, would be between 30 minutes and
1 hour. Therefore, a hypothetical environmental situation similar to
the heavily polluted nighttime conditions found in Los Angeles,
California (i.e., 200 ppb NO, 20 ppb N02» 13,000 ppm 1^0, and 50 ppb
HNO2) has been calculated to induce a 6 percent/hour conversion of a
nitrosatable amine to its N-nitroso derivative (47). However, under
conditions of low pollution, it was estimated that the nitrosation would
not occur.
It was concluded from the experimental data that release of di-
methylamine into a heavily polluted atmosphere could result, after
nitrosation during darkness, in the formation of appreciable concen-
trations of dimethylnitrosamine. This nitrosation should, according
to experimental data, diminish rapidly as a result of the photolysis
of the nitrous acid during daylight. The concentration of DMN would
decrease due to this decreased nitrosation as well as via photodegradation
31
-------
of the DMN at an approximate rate of 50 percent per hour. A compila-
tion of experimental, natural, and hypothetical reactions is presented
in Table IV.
B. TOXICOLOGY AND CARCINOGENICITY
decomposition before becoming active carcinogens (24). This transfor-
mation is generally thought to be by an enzyme system similar to the
microsomal drug-hydroxylating system (20). Conversion to reactive
intermediates during cellular metabolism has been illustrated with
oxidation playing a decisive role (48):
*Nicotinamide-adenine-trinucleotide-phosphate
Other hypothetical pathways for the metabolism of nitrosamines
which would produce carcinogenic metabolites have emerged. The follow-
ing pathway for the metabolism of nitrosamlnes was proposed after in-
vestigations of several years (49-52). Enzyme hydroxylation at the
a carbon in one of the aliphatic chains occurs in dialkylnitrosamines.
Further oxidation can produce the acylalkylnitrosamide, while hydrolysis
produces the monoalkylnitrosamine and an aldehyde. Until recently, it
was conjectured that the monoalkylnitrosamine was rearranged into its
diazohydroxide counterpart, which then becomes diazoalkane and then
1. General
Nitrosamines are generally believed to require enzymatic
TPNH* *
32
-------
TABLE IV
CONDITIONS FOR NITROSAMINE FORMATION
IN THE ATMOSPHERE
EXPERIMENTAL CONDITIONS
HYPOTHETICAL
POLLUTED CONDITIONS
A. In Room Air At Normal Temperature
• Amine 1.0 ppm
• Nitrous Acid Vapor 0.5 ppm
• NO 2.0 ppm
• NO„ 2.0 ppm
• H2u 13,000.0 ppm
Usine Dimethylamine 4%/Min. N-Nitrosodimethylamine
Maximum Rate Constant = 0.1/ppm/minute
B. • In Dry Nitrogen
• Amine 1.0 ppm
• NO2 1*0 ppm
• NO 4.0 ppm
Usine Dimethvlamine 1%/Min N-Nitrosodimethylamine
• Reaction N0x Dependent
C. • Amine 1 ppb
• Nitrous Acid Vapor 50 ppb
• NO 200 ppb
• N02 20 ppb
• H20 13,000 ppb
Calculated 6%/Hour Conversion of
Amine to Nitrosamine
NATURAL CONDITIONS
D. • Amine
• Nitrous Acid Vapor - Not Stable,
Rapidly Forms Nitric Acid
• NO 2.0 ppb
• N02 4.0 ppb
• HO 16,000.0 ppb At
2 50% Humidity
Source: Dr. Phillip Hanst, U.S. Environmental Protection Agency, Research Triangle Park, North
Carolina.
-------
the carbonium ion, which can alkylate nucleic acids. However, in the
case of DMN, alkylation is transmethylation with no hydrogen atom ex-
change involved in driving the methonium ion (53). This would argue
against the intermediate formation of diazomethane during DMN meta-
bolism. Administration of diethylnitrosamine (DEN) has resulted in
ethylation of nucleic acids which supports a-oxidation of one ethyl group
and transethylation of the other. Two alternate schemes for transmethyl-
ation of guanylic acid can be illustrated as follows (53):
CD^ D ^CD2N2 >CD2H > CD^H-guanine me/e 167
3-oxidation of dialkylnitrosamines has also been theorized. The
first step requires enzymatic dehydrogenation between the a and 3 car-
bons of one alkyl chain. Adding water to the double bond produces the
3-hydroxylated nitrosamine. Continuation of the oxidative process
would yield acetyl-CoA and methylalkylnitrosamine from the hydroxylated
nitrosamine. The methylalkylnitrosamine could then undergo fJ-oxida-
tion which would produce either the methonium ion or the carbonium ion
corresponding to the second alkyl group (55).
Alkylation of nucleic acid, particularly of the 7 position of
guanine appears to be closely associated with acute toxic tissue
injury, but the mechanism is not clear. Messenger RNA methylation as
Enzyme
*
CD^ * CD^ - guanine m/e 168
cd3
34
-------
a result of DMN poisoning effectively inhibits translation during pro-
tein synthesis by inactivating guanine in the genetic code (56-58).
This may be one mechanism of toxicity, mutagenicity, or carcinogenicity;
however, polyribonucleotides with 7-methylguanylic acid have been
shown to function as normal RNA polymerase templates (59). Incorpora-
tion of 3-methylcytosine in polycytidylic acid not only lowers template
efficiency in polyguanylic acid production, but cdn also produce
incorrect guanylic and uridylic acid polymers. Therefore, alkylation
at the 3 position of cytosine may be more closely associated with carcino-
genesis than 7-position alkylation of guanine-
There appears to be a lessening of carcinogenicity when the hydro-
gen on the carbon atoms adjacent to the nitroso group is replaced by
deuterium, and almost complete inhibition of carcinogenic activity
when these hydrogen atoms are replaced by methyl groups. However,
methyl groups in other positions seem to enhance the compound's car-
cinogenicity, while chlorine or bromine substitution in these other
positions renders the compound even more active (60). In another
evaluation of the relationship between compound structure and acute
toxicity, the acute toxicological effects of the dialkylnitrosamines
appeared to decrease with chain length. The cyclic nitrosamines, e.g.,
N-nitrosohexamethyleneimlne and N-nitrosomorpholine, have also been
reported to be acutely toxic (20).
The potency of nitrosamines in causing acute tissue injury and
death has been shown to vary considerably. Single-dose oral LD^q's
35
-------
have been shown to range from 18 mg/kg for methylbenzylnitrosamine to
greater than 7.5 g/kg for ethyl-2-hydroxyethylnitrosamine. LD^'s of
17 nitrosamines are presented in Table V.
The histopathological effects of acute nitrosamine poisoning
have not been critically examined for many of the compounds other than
dimethylnitrosamine and diethylnitrosamine. These two compounds are
effective hepatotoxins causing centrilobular necrosis and hemorrhage
within 24 to 48 hours. Death follows within three to four days or
the animals survive and recovery is complete within three weeks (20).
Nitrosamines appear to induce specific systemic effects involving
specific organs, i.e., nitrosopiperidine produces esophageal cancer
in rats whether administration is oral or intravenous (60). The total
dosage required for carcinogenic development is often affected by the
time involved. If there is a latent period, the smaller the daily
dose, the smaller the total dose administered by the time of appearance
of the cancer. It is, therefore, possible that there exists no thres-
hold dose, only that the animals may die of other causes without
tumor development before the latent period ends (48).
Nitrosamines can induce tumors in many body tissues. Of the
approximately 100 N-nitroso compounds studied, more than 80 have
been shown to be carcinogenic in test animals (61). Some of these
have produced carcinogenic effects after administration of a single
dose (62). Table VI contains a compilation of some of these sites
*tc
This class of compounds includes nitrosamines, nitrosamides, nitroso-
ureas, etc.
36
-------
TABLE V
ACUTE TOXICITY OF SOME NITROSAMINE COMPOUNDS
Compound
LD50*
Reference
Dimethylnitrosamlne
27-41
63
Diethylnltrosamine
216
63
Di-n-propylnitrosamine
>400**
64
Di-n-butylnitrosamine
1200
65
Di-n-amylnitrosamine
1750
66
Methyl-n-butylnltrosamine
130
63
Methyl-t-butylnitrosamine
700
63
Ethyl-n-butylnitrosamlne
380
67
Ethyl-t-butylnitrosamine
1600
67
Ethyl-2-hydroxyethylnitrosamine
>7500
67
Di-2-hydroxyethylnitrosamine
>5000
68
Methylphenylnitrosamine
200
63
Me thylb en zyIni t ro samine
18
67
Nitrosoroorpholine
282
66
N i t ros ohexamet hyleneimine
336
69
Nitrosohept ame thy1eneimine
283
70
Nitrosooctamethyleneimine
566
70
LD^units: mg/kg, single oral dose, adult male rats
Male and female Syrian golden hamster.
37
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TABLE VI
TUMOR SITES OF SOME NITROSAMINES
u>
00
Compound
Target Organ
Reference
Dimethylnitrosamine
Liver
78
Nasal sinus
77
Kidney
79
Diethylnitrosamine
Liver
61
Nose
80
Lung & Bronchi
81
Di-n-propulnitrosamine
Liver
61
Di-isopropylnitrosamine
Liver
61
Di-n-butylnitrosamine
Liver & Uninary Bladder
82
Butyl-butanol-n-nitrosamine
Liver & Urinary bladder
61
Di-pentyl-nitrosamine
Urinary bladder*
61
Liver**
61
Dibenzylnitrosamine
Lung*
61
**
61
Diphenylnitrosamine
**
61
Methyl-vinyl-nitrosamine
Esophagus
61
Methyl-pentyl-nitrosamine
Esophagus***
61
Methyl-benzyl-nitrosamine
Esophagus
61
Ethyl-butyl-nitrosamine
Esophagus
61
NO-sarcosine ethyl ester
Stomach, esophagus
61
Methyl-allyl-nitrosamine
Kidney
61
Ethyl-tert-butyl-nitrosamine
**
61
-------
TABLE VI (Continued)
Compound
Target Organ
Reference
N-nitrosomorpholine
T . ***
Liver
Blood vessels
61
83,84
Nitroso-pyprolidine
Liver
61
Nitroso-piperidine
Esophagus* ** ***
Nasal cavity* ***
61
61
Di-nitroso-piperazine
Esophagus* **
61
N-nitroso-n-carbethoxy-piperazine
Liver
61
N-nitroso-n-methy1-p iperaz ine
**
61
N-nitroso-proline-ethylester
**
61
Nitrosomethylurethane
Pancreas
85
Nitrosohexamethyleneimine
Tongue
69
Nitrosoheptamethyleneimine
Esophagus
70
~Subcutaneous administration
**Oral administration
***Intravenous administration
-------
with the corresponding nitrosamine administered. Nitrosamines have
also appeared to transplacentally induce neoplasms. Subcutaneous
administration of dimethylnitrosamine to pregnant rats during the
ninth to fifteenth day of gestation resulted in nearly half the off-
spring developing tracheal papillomas within 25 weeks of the first
exposure (71). Induction of esophageal papillomas was reported within
7 weeks of treatment with 200 mg N-nitrosoheptamethyleneimine, a much
more rapid progression (70).
The site for tumor induction appears to correlate well with site
of metabolism (72). Rat liver readily metabolizes dimethylnitrosamine,
while kidney and lung do not function as well. Liver tumors are more
frequently induced with DMN, with renal tumors reported only occasion-
ally and lung tumors only under special controlled experimental con-
ditions (73). Administration of diethylnitrosamine in hamsters sup-
ports the correlation between metabolic site and tumor development.
Hamster lung readily metabolizes DEN, while the liver is not as adept,
yielding a corresponding higher frequency of induced lung tumors than
liver tumors. One small consolation in the carcinogenicity data
available has been the inability to induce carcinogenic effects by
feeding nitrosohydroxyproline and nitroproline, N-nitroso derivatives
of two commonly occurring food amino acids (74-76).
The nitrosamines are not mutagenic when applied to in vitro
bacterial systems; they appear to require metabolic activation by
mammalian enzyme systems. This was demonstrated using DMN in a
40
-------
host-mediated microbial assay (86) and in a liver microsomal-activated
microbial system (87) . Mammalian systems have also failed to respond
to mutagenic activity. In a dominant lethal test performed by exposing
males to the compound in question followed by subsequent mating with
untreated females, DMN did not produce any mutations. This lack of
mutagenicity was thought to be due to the inability of the male germ
cells to metabolize and activate the compound (88,89).
2. Humans
A report of the accidental dimethylnitrosamine poisoning
of two men employed by an automotive production facility where the com-
pound was used as a solvent was published in 1956 (90) . One of the men
recovered after exhibiting signs of liver damage. The other died after
an accident, and at necropsy a cirrhotic liver with regenerating nodules
was revealed. An additional report of the hepatotoxicity of DMN in-
volved three men using the nitrosamine for 10 months as a solvent in
a British industrial research laboratory. Two of the three men re-
ported signs of liver injury, one of which was confirmed as cirrhosis
upon necropsy after death from bronchial pneumonia. The other tech-
nician , who had experienced a hard liver with an irregular surface,
recovered after termination of exposure.
Dimethylnitrosamine, p-nitroso-N, N-dimethylaniline, and N,4-
dinitrosomethylaniline (Elastopar ) have been indicated as possible
agents perpetuating a higher than normal mortality rate from bile
duct and salivary gland cancer in rubber factory workers (91).
41
-------
Multiple exposures to many compounds occur during industrial exposure;
therefore, it cannot be concluded that these were the causative agents
in these cases.
Reports have indicated that nitrosamines are carcinogenic in that
they are metabolized in vivo to an active carcinogen. Comparable rates
of in vitro metabolism with accompanying similar nucleic acid methyla-
tion levels were observed using human and rat livers exposed to dimethyl-
nitrosamine (72). This provides another suggestion for the suscepti-
bility of man to nitrosamines, presenting the possibility of a response
similar to that of the many other organisms that have succumbed (92).
3. Animals
The vast majority of the direct biological evidence re-
ported for the carcinogenicity of nitrosamines has been gathered using
laboratory animals. The evidence for carcinogenicity in man is only
indirect. Studies have shown nitrosamines to be versatile in their
induction of organ tumors with practically all locations reported as
the target of at least one compound (24). The versatility of action
is enhanced by the many different species, including subhuman primates
that have been experimentally affected by the carcinogenic properties
of nitrosamines. One compound, diethylnitrosamine, has axhibited an
effect in rat, mouse, hamster, guinea pig, pig, rabbit, dog, rainbow
trout, aquarium fish, grass parakeet, and monkey (61). Oral adminis-
tration is an effective method of dosage, with small daily doses
over an extended period being more effective than large single doses
42
-------
(60). To date, no animal species has shown resistance to the carcino-
genic action of the most potent N-nitroso compounds, which leads to
the real possibility that man could also be affected (73,93).
Heptamethyleneimine, a secondary amine fed in conjunction with
nitrite, has induced lung and esophageal cancer in over 60 percent of
the tested animals, indicating a possible contribution to lung cancer
in smokers from nitroso compounds formed from amines in swallowed
tobacco smoke and nitrite in food (60).
Isolated instances of inhalation studies conducted on experimental
animals are found in the literature. Tumors of the nasal cavities and
kidneys resulted from single or repeated inhalations of DMN in rats
(93) . Spray inhalations of a dilute aqueous solution of DEN (1:250)
produced after four months a 50 percent incidence of liver carcinoma
in rats (81) . Tracheal and lung tumors were induced in hamsters after
spray inhalations of 1-2 mg DEN occurring twice weekly for five months.
Inhalation of methylbutylnitrosamine has induced throat cancer in
rats after 23 weeks of exposure to 70 to 200 mg/kg (94). Table VII
contains a listing of suspected carcinogenic nitrosamines. A compila-
tion of compounds tested and found lacking in tumor production is
contained in Table VIII.
C. MEASUREMENT TECHNOLOGY
Many studies of analytical procedures employed for nitrosamines
have been reported in the literature. Each investigator has developed
his own procedure or at least has added sophistication to existing
43
-------
TABLE VII
NITROSAMINES THAT HAVE BEEN TESTED AND
FOUND TO BE CARCINOGENIC
Dimethylnitrosamine
Diethylnitrosamine
Di-n-propylnitrosamine
Di-iso-propylnitrosamine
Di-n-butylnitrosamine
Di-amylnitrosamine
Methylethylnitrosamine
Methylvinylnitrosamine
Methylallylnitrosamine
Methylamylnitrosamine
Methylcyclohexylnitrosamine
Methylheptylnitrosamine
Methylphenylnitrosamine
Methylbenzylnitrosamine
Methylphenylethylnitrosamine
Methyl-4-methylamino-azobenzolnitrosamine
Dimethyldinitrosoethylenediamlne
Ethylvinylnitrosamine
Ethylvinylisopropylnitrosamine
Ethylvinyl-n-butylnitrosamine
Butylamylnitrosamine
N-nitroso-pyrrolidine
N-nitroso-piperidine
Dinitroso-piperazine
N-nitroso-n'-methylpiperazin
N-nitroso-n'-carbethoxy-piperazin
N-nitrosomorpholine
N-nitrosoindolinN-nitrosomethylamine-sulforan
N-nitroso-phenylhydroxylamine
N-nitrosotrimethylhydrazin
N-nitrosoethylethanolamine
N-nitrosodiethanolamine
N-nitroso-b is(acetoxyethyl)amine
N-nitroso-butanol-(4)-butylamine
N-nitroso-2-chlorethyl-methylamine
N-nitroso-acetonitril-methylamine
N-nitroso-di-acetonitrilamine
N-nitrososarcosine
N-nitrososarcosine-ethylester
N-nitroso-l,l-dimethyl-butanon-(3)-methylamine
N-nitroso-4-picolyl-ethylamine
Butanol(4)-butylnitrosamine
44
-------
TABLE VIII
NITROSAMINES THAT DID NOT PRODUCE TUMORS WHEN TESTED
Diallylnitrosamine
Dicyclohexylnitrosamine
Diphenylnitrosamine
Dibenzylni t ros amine
Ethylvinyl-tert.butylnitrosamine
Tri-nitroso-tri-methylenetriamine
N-nitroso-N-methyl-O-methyl-hydroxylamine
45
-------
methods . As a result, confusion has arisen concerning the quantita-
tion and identification of nitrosamines from one publication to the
next (11) .
Until recently, detection of nitrosamines at the low environmen-
tal concentrations expected has been difficult. This difficulty
arises from some of the general properties of these compounds:
1) they do not fluoresce, 2) they do not have well-defined absorption
spectra, and 3) they are difficult to separate from other analysis-
interfering compounds (nitrogen-containing compounds) (21) . Other
problems due to state-of-the-art methodologies which, hopefully, will
be remedied include the following (7):
(1) The need for analytical detection and quantification pro-
cedures for secondary amines and nitrosating agents,since
nitrosamines are formed from these precursors;
(2) The vast majority of the nitrosamines are non-volatile and
are, therefore, not as readily detectable as the volatile
compounds . Improved and innovative sample clean-up proto-
cols could possibly afford the researcher comparable
non-volatile and volatile detection limits;
(3) Development of a field test which could accomplish a
pre-screening to reduce the number of samples that must be
definitively assayed.
46
-------
1. Detection of Volatile Nitrosamines
Conclusive evidence of the existence of atmospheric
nitrosamines has only recently become available (95) . Consequently,
the methodology for nitrosamine analysis has been developed primarily
for the analysis of food samples. All the nitrosamines reported in
food products to date are classified as volatile (10) . This property
permits preliminary sample cleanup by distillation with subsequent
isolation and separation procedures, such as solvent partitioning
and/or thin-layer, column, and gas-liquid chromatography,
a. Initial Separation from Product
The determination of trace components in foods is
complicated by the fact that the components must initially be
removed from the food matrix before they can be measured. In many
food analyses, the efficiency of this step is often the limiting
factor in the success of the procedure (92).
The term "steam distillation" has frequently been used to describe
the distillation of nitrosamines from an aqueous system. Scanlan (92)
argues that this term is partially incorrect as steam distillation
refers to a procedure in which the component being distilled is
immiscible with water. Hence, the water and the immiscible component
exert their vapor pressure independently.
Distillations at atmospheric as well as at reduced pressures
have been widely used to remove nitrosamines from foods, although
higher recoveries have been reported for vacuum distillation in
47
-------
comparative studies (96) . Satisfactory recoveries have been obtained
from neutral, alkaline, and acid media (see Table IX). Eisenbrand
et al. (97) found that distillation from a 0.2 N acid medium did not
result in hydrolysis of nitrosamines and suggested that this would
provide an effective means of separation from interfering base con-
taminants. They added, however, that since foods may contain nitrate,
distillation from alkaline medium should be carried out before distil-
lation from acid to avoid nitrosamine formation from amines at low pH.
Due to the favorable partition properties for nitrosamines,
dichloromethane has frequently been used for extractions from food
and aqueous distillates (96, 98-102). Many investigators saturate the
aqueous phase with an inorganic salt (e.g., Nacl, Na2S0^) to increase
the effieicney of the extraction. Issenberg and Tannenbaum (103)
described a modified Likens and Nickerson (104) apparatus which con-
tinuously distilled the nitrosamines from the food and extracted the
nitrosamines from the distillate in one operation,
b. Clean-up Procedures
Both aqueous distillates and dichloromethane
extracts often contain a variety of contaminating components which
can interfere in the subsequent analysis of nitrosamines (92). A
number of thin-layer and column chromatography clean-up procedures
have been used to remove or reduse the level of these contaminants
(98-100, 105-107). Eisenbrand (106) reported that excellent recoveries
are obtainable with thin-layer chromatography if precautions are
48
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TABLE IX
RECOVERIES (It) OF DIALKYL-, HETEROCYCLIC, AND ALKARYL-N NITROSAMINES
BY DISTILLATION FROM NEUTRAL, ALKALINE, AND ACID MEDIA1
NITROSAMINE
MEDIUM
WATER
0.2
N NaOH
0.2 N TARTARIC ACID
PRESSURE
REDUCED
ATMOSPHERIC
REDUCED
ATMOSPHERIC
REDUCED
ATMOSPHERIC
I Di-aethyl-nitrosamine
94
101
94
98
98
101
II Di-ethyl-
101
98
101
99
100
97
III Di-n-propyl-
98
96
99
98
100
97
IV Di-iso-propyl-
100
100
99
100
99
98
V Di-n-butyl-
100
96
100
98
100
100
VI Di-n-pentyl-
100
99
100
100
100
100
VII Di-n-hexyl-
98
99
100
100
96
99
VIII Di-n-octyl-
45+
93
43+
95
30+
93
IX Methyl-vinyl-
94
90
89
89
88
78
X Hethyl-n-butyl-
100
96
99
96
100
99
XI Methyl-n-pentyl
99
96
101
96
100
97
XII Methyl-n-heptyl-
98
97
99
98
99
97
XIII Methyl-benzyl-
96
94
98
96
94
92
XIV N-Nitroso-pyrrolidine
89+
71
100+
85
67+
71
XV K-Nitroso-piperidine
98
97
100
99
97
98
XVI Methy1-2-hydroxyethyl-nitrosamine
29+
29
27+
14
16+
—
1 Distillation volume was 6 ml with the exception of +, where the volume was 10 ml. Results given are the means of at least two
de terainat ions.
Source: Eisenbrand, G.A., A. von Hodenberg, R. Preussman, "Trace analysis of N-nitroso compounds. II. Steam distillation,"
Z. Anal. Chea., 251, 1970.
-------
taken to prevent losses from volatilization and exposure to light.
During separations carried out at 4°C under light protection, values
of better than 90 percent recovery were noted. Some of the column
chromatographic procedures described have employed silica-gel (98),
acid-treated Florisil (105), polyamides (100), or polymer beads (101).
Telling (99) reported a method in which nitrosamines were purified
on an alumina column after dichloromethane extraction, oxidized to
nitramines, and re-chromatographed on a magnesium oxide/alumina
column for further purification.
c. Separation and Detection Techniques
A frequently used method for the separation and
subsequent detection of nitrosamines has been thin-layer chromatography
followed by spraying with Griess , ninhydrin, or palladium (II)
chloride/diphenylamine spray reagents (108,109). However, there is
not general agreement as to the effectiveness of TLC methodology for
this purpose (110,111). One strong objection is the fact that a
number of substances with values* similar to those of nitrosamines
could be erroneously identified as nitrosamines (10) .
Several colorimetric procedures have been reported (112-114),
although none seem to have the required specificity for nitrosamines.
These methods generally involve photolytic splitting of the N-N bond
with use of the Griess reagent to measure the nitrite formed from
*A ratio determined by the distance traveled by the spotted compound
to the distance traveled by the solvent front.
50
-------
the nitrosamine. Ultraviolet spectrophotometric determinations have
been attempted, but can only be performed on relatively pure nitro-
samine solutions (115) . Extracts from foods frequently contain some
interfering substances despite initial separation and clean-up
procedures; therefore, ultraviolet spectrophotometry is not conclusive.
Polarography has been used in the determination of nitrosamines
(116) and although this is a sensitive technique, it lacks the
specificity required for identification (117) . In an effort to
improve selectivity, a method has been described which involves the
differential polarography of nitrosamine solutions before and after
photolysis (118) . The nitrosamine concentration in the presence of
light stable contaminants was estimated by difference; however, com-
pounds which could be confused polarographically with nitrosamines,
such as unsaturated aldehydes, were also labile to short wavelength
radiation.
Gas-liquid chromatography (GLC) has been used with reliability
for detecting and quantitating nitrosamines. The specificity of
response has been increased by the use of GLC detectors that are more
selective than the conventional flame ionization detector (FID). Al-
though the FID has been used to determine nitrosamines in moderately
clean extracts (84,119,120), it lacks tha specificity necessary to
determine nitrosamines in extracts from foods (2). The alkali flame
ionization detector (AFID) gives a good response to volatile nitro-
samines, but requires a very lengthy and rigorous clean-up procedure
51
-------
(10). The Coulson electrolytic conductivity detector (CECD) gives
good responses in the pyrolytic mode for simple aliphatic nitrosamines
(121,122) but poor responses for cyclics (e.g., nitroso-pyrrolidien)
(119). The CECD used in the reductive mode, however, seems to work
well for most volatile nitrosamines tested including cyclics (119) .
The microcoulombic detector has received limited use but seems to offer
results similar to the CECD operated in the reductive mode (123).
Because of their selectivity and the minimum requirements for clean-
up , both of these latter detectors offer distinct advantages for
large scale screening of food products.
It is generally agreed that the best method for the identifi-
cation of nitrosamines is mass spectral analysis in conjunction with
gas chromatography (2,10,11,124,125). However, mass spectral methods
determine conformation rather than quantitation and, due to sophisti-
cation and expense, can be unsuitable for individual laboratories (125).
2. Detection of Non-Volatile Nitrosamines
Methods for the determination of non-volatile N-nitroso
compounds have not been developed as extensively as thoae for volatile
nitrosamines (125) . As stated earlier, much of the methodology for
nitrosamines has been developed for food analysis and, unlike the
volatile nitrosamines , the non-volatile compounds possess no single
property which allows their separation from the food matrix (2). This
has made the development of methods for their estimation exceedingly
difficult.
52
-------
Since nitrosamines may be formed when primary amines, secondary
amines, tertiary amines , and quaternary ammonium compounds react
with nitrite, it is reasonable to assume that a number of the nitro-
samines formed would be non-volatile, e.g., nitrosamines formed
from the free amino acids proline, hydroxyproline, and sarcosine.
Judging from the wide variety of complex secondary amines occurring
in nature, a large group of naturally occurring high molecular
weight compounds can be expected.
Lunt et^ al_. (126) and Walters et^ ajL. (127) have reported a
method in which non-volatile nitrosamines were converted to volatile
derivatives which could be measured. The nitrosyl chloride was
volatilized from the dichloromethane with nitrogen, trapped in
alkali, and determined as inorganic nitrite. The procedure was
designed to give a total value for non-volatile N-nitroso compounds
and would provide no information regarding the identity or the amounts
of individual nitrosamines. Nevertheless, it provides a screening
method which allows for the detection of nitrosamines .
In addition to the GC-TEA, described in Section C.3, a high per-
formance liquid chromatograph interfaced to a thermal energy analyzer
has been developed which can detect nanogram amounts of non-volatile
nitrosamines (127) . As solvent containing the N-nitroso compound
elutes from the liquid chromatograph, it is directed into a heated
catalytic pyrolyzer. The liquid is atomized into small droplets and
these are vaporized by the pyrolyzer. During this vaporization, the
53
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N-nitroso compounds rupture at the N-NO bond, splitting off the
nitrosyl radical. This radical then reacts with ozone, forming elec-
tronically excited nitrogen dioxide which quickly decays to ground
state, emitting light. The intensity of this emission is directly
proportional to the number of moles of N-nitroso present. Approxi-
matley 20-50 nanograms of the N-nitroso compound are required for
detection, with all N-nitroso compounds tested detectable. Although
this is 1000 times less sensitive than the GC counterpart, it can be
used for selective mg/kg analysis of non-volatile N-nitroso compounds
(127) .
3. Detection of Atmospheric Nltrosamines
As previously indicated, technology for the detection
and measurement of nitrosamines has been developed primarily for
assessment of food and biological samples. The recent detection of
ambient atmospheric dimethylnitrosamine and the possibility of
secondary formation of ambient nitrosamines underscore the need for
more research in the area of ambient nitrosamine analysis.
Most of the commonly used procedures for detection of trace
organic compounds in air are non-specific. They are designed to
measure classes of compounds rather than to identify or quantitate
individual components. While these methods ire adequate for some
purposes, more detailed information is often needed to evaluate the
significance of pollutants, particularly in the case of nitrosamines.
54
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Most methods for identifying and measuring trace levels of
individual organic components in air require a prior concentration
step. Frequently used procedures are solvent scrubbing, condensing
with cold traps, or collecting on charcoal. Each of these techniques
has major limitations (128).
To achieve adequate sensitivity with most solvent scrubbing
trains, the solvent containing the pollutants must be reduced in
volume, typically by evaporation. This can be accomplished with
minimal sample loss for high-boiling pollutants, but significant
losses occur when volatile components are involved.
Use of a cold trap has the disadvantage of freezing out water
along with the organic materials. At 25°C and 50 percent relative
humidity, one liter of air contains over 11 mg of water vapor. Thus,
in typical ambient air, water is the major component, excepting the
fixed gases. A cold trap condenses organic pollutants with much
larger quantities of water, usually resulting in two-phase systems
requiring special handling.
A report of positive atmospheric nitrosamine detection was
negated after detection of nitrosamine production, within the cold
trap, after sampling only 0.5 ppm dimethylamine and 0.5 ppm NO in
air (129). Cold trap artifact formation yielded 0.05 ppb DMN which
3
was determined to be equivalent to a level of 0.15 (jLg/m in the
atmosphere (130) .
55
-------
The possibility of this occurring during any cold trap monitor-
ing was also investigated by Fine (129). Concurrent samplings of
paired cold traps, one with added dimethylamine and one without, were
repeated three times in Baltimore, Maryland. The first one-hour
sampling revealed identical levels of 3.3 (J.g/m DMN formed, indicating
no artifact formation. Detection in the second pair of samples of
16 (j-g/m3 in the dimethylamine (DMA) spiked cold trap and 12 )ag/m3 in the
control trap may indicate results that are within acceptable experi-
mental deviations. Likewise, a third sampling allowed determination
3
of 2.1 p.g/m DMN in the cold trap with DMA while the control cold trap
3
had a concentration of 1.9 (ig/m DMN. In this series of experiments,
it was also determined that addition of nitrite to the traps did not
affect DMN production.
Artifact formation testing in Tenax was conducted by Dr. Pelllzzari
at Research Triangle Institute, North Carolina. In a series of re-
plicate experiments, it was determined that NO/NC^ in concentrations
of 10 ppm or more spiked into an air stream containing purified DMA
can nitrosate the amine to DMN. Concentrations of 1 ppm or less pro-
duced undetectable quantities. In this same experimental •equence,
it was found that spiking of the air stream with purified dimethyl-
amine from a permeation tube did not produce detectable DMN (131).
Therefore, the artifactual formation of DMN during monitoring cannot
be completely negated; however, it does appear that only small quanti-
ties of the DMN found can be attributed to this type of formation.
One explanation for artifact formation that has been previously
56
-------
noted could be the presence of DMN in the dimethylamine utilized
during experimentation. Dr. Pellizzari found low concentrations of
DMN in a laboratory sample of DMA (10 ppm) while Dr. Pine found 20 to
30 ppb DMN on a weight/weight basis in liquid in a DMA sample from
the Belle, West Virginia Dupont production facility (129).
Cryogenic condensing of entire air samples, including oxygen
and nitrogen, followed by later processing to isolate the organics
may be a promising method, although special equipment is needed to
carry out analyses using this scheme.
Charcoal can be used to quantitatively remove organics from
air. However, recovery of the collected components from the charcoal
is usually incomplete and variable. Charcoal may also serve as a
catalyst to promote alteration of the sample.
Mieure and Dietrich (128) have described a method for trapping
organics from air which involves the use of gas chromatography column
packings. Because of their ability to greatly retard the progress
of organics through a column, porous polymer bead packings are partic-
ularly well adapted to this purpose. Air to be sampled is drawn
through a column containing packing material at ambient temperatures.
Under these conditions, the organics in the air are retained but
water is not. These columns can actually be considered to be GC
columns operated at ambient temperature. In this context, alt Is
the carrier gas and also the means of continuous sample induction.
Individual components elute through these columns at a rate
57
-------
proportional to the interaction with the packing. By using short
(4-6 inch) collection columns, high flow rates (0.5-2 liters/min.)
are possible with inexpensive, portable vacuum pumps. This permits
short sampling times and/or maximum sensitivity. By connecting the
collection column directly into the GC, the entire sample is chroma-
tographed, again allowing maximum sensitivity. Using a sensitive
flame ionization detector capable of detecting 10 nanograms, components
3
measured at 0.5 g/m can be measured. Sampling larger volumes of
air will give proportionally lower detection limits (128).
Fine and Rounbehler have recently reported a detection technique
combining thermal energy analysis with gas chromatography (132-134).
The new GC-TEA method is highly specific to heat-labile nitrosyl
groups. After discussions with several field experts, it is apparent
that this procedure is the most promising as a candidate for a univer-
sally accepted technique. This method appears to have the most acute
sensitivity reported, with the possibility of analysis, by direct in-
jection, of solutions containing less than 1 ng/ml N-nitroso compounds.
This sensitivity and the selectivity for nitrosyl groups are major
advantages over the GC-Coulson electrolytic conductivity detector and
the GC-alkali flame ionization detector techniques. In addition,
there is little need for time-consuming clean-up or concentration
procedures. Concentration is generally unnecessary and clean-up Is
only required to ensure that the extract is compatible with the GC
column. No clean-up whatsoever is required for the TEA detector.
58
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The method proceeds in the following manner (see Figure 5):
1. After introduction of the sample into the injection port with
subsequent separation by the chromatograph column, the TEA
pyrolyzer splits off the nitrosyl radical from N-nitroso
compounds:
R R
^ N-N-0 > N *+ *N-0
l/ l/
R R
(R and R^" may be any organic radical)
2. The effluent is expanded through a narrow constriction into
an evacuated reaction chamber where the nitrosyl radical is
subsequently reacted with ozone, yielding electronically
excited nitrogen dioxide:
'N-0 + 03 > N0*2 + 02
3. The excited nitrogen quickly returns to ground state, emitting
light in the near infrared region of the spectrum:
N02* > N02 + hv
This light is monitored by an infrared-sensitive photomulti-
plier tube, with the emission intensity proportional to the
number of nitrosyl radicals present (132).
There are four primary advantages of GS/TEA over other
methods, and the first of these involves quantitation ability.
Calibration is linear over five orders of magnitude with GC/TEA;
therefore, quantitative analysis at the <3 ng/ml N-nitroso compound
concentration level Is definitely possible.
59
-------
OZONE
TEA
CATALYTIC
PYROLYZER
RED FILTER
REACTION
CHAMBER
GC
CARRIER
GAS
RESTRICTION
HEATED
PTFE TUBE
250° C
INJECTION
PORT
VACUUM
PUMP
PM TUBE
FIGURE 5
SCHEME OF GC-TEA INTERFACE
60
-------
-12
A practical detection sensitivity of 1 x 10 moles N-nitroso
compound is the second advantage of GC/TEA, but even greater sensi-
tivity can be realized if the solvent is removed. If existing clean-
up and concentration procedures are incorporated, detection by
13
direct injection at the 5 part/10 concentration level is possible.
The TEA detector determines the selectivity because it requires
that a compound be catalytically pyrolized at a low temperature to
give a nitrosyl radical which will react with ozone to produce infra-
red light. Although luminescence is also produced by other compounds
during an ozone reaction, the emissions are in the blue or visible
spectrum. This specific selectivity constitutes the third advantage
of the GC/TEA over other methods. Despite the fact that other com-
pounds or functional groups might react with ozone to produce an
infrared luminescence, none have yet been found. See Table X for
a list of compounds that have been tested for interference on the TEA.
In the event of such interference, the effect may be eliminated by
interposing a cold trap between the catalytic pyrolyzer and the ozone
reaction chamber (134) .
The solvent front, which can be observed on the chromatogram,
displays three distinct effects. There is an initial sharp positive
peak, followed by a broad negative peak which overshoots the baseline
in a positive direction before decaying back to the baseline. A cold
trap, placed as previously discussed and maintained at a temperature
of -15°C, eliminates the negative peak completely (135). This
61
-------
TABLE X
ANALYZED COMPOUNDS WHICH WERE FOUND TO GIVE NO INTERFERENCE ON THE TEA
Acetic acid
Ethyl carbamate
Oxalic acid
Acetone
Ethylene glycol
n-Pentane
Acetonitrile
Fluorobenzene
Phenyl hydrazine
Alizarin red
Gasoline
d,1-Phenylalanine
Ammonia (gas)
Glycyrol
p-Phenyl-azoaniline
Benzene
d-Glucose
Phosphoric acid
Benzylsalicylate
Glutamic acid
Propane (gas)
2-Butoxy ethanol
n-Hexane
Pyridine
Carbon dioxide
Hydrogen (gas)
Quinine
Carbon disulfide
Hydroquione
Sodium acetazolamide
Carbon monoxide (gas)
8-Hydrozyquioline
Sulfadiazine
Carbon tetrachloride
Inosine
Sulfanilic acid
Chloral hydrate
d,l-iso-leucine
Tetrahydrofuran
Chlorobenzene
Methane (gas)
Theophylline
1-Chloropropane
Methyl acetate
Toluene
2-Chloropropane
N-Methyl bisacrylamide
2,4,6-Trichlorophenol
Cyclohexane
2-Methyl butane
2,2,4-Trimethylpentane
Cyclopentane
Methyl formamide
d,1-Tryptophane
1,2-Dichloroethane
Methyl isobutyl ketone
Urea
2,3-Dichloropropane
Methyl orange
Uric acid
Diethylether
Methyl red
Urethane
Dimethylamine (gas)
Naphthalene
Water
p-Dioxane
Nitrogen (gas)
Xylene
Diphenylamine
Nitrobenzene
Ethyl acetate
o-Nitrotoluene
62
-------
simplifies quantitation of early peaks and comprises the fourth ad-
vantage of the GC/TEA methodology (132) .
Although Dr. Fine does not use any method of confirmation for
the detection of nitrosamines in conjunction with GC/TEA, it is gen-
erally accepted procedure for all other detection methods to confirm
detection with mass spectrometry. A high-resolution, sensitive
apparatus can be a most acceptable and satisfactory means of confirma-
tion. Dr. Fine's technique has been tested in parallel with GC/MS
techniques and at this time appears to be quite reliable.
D. AMBIENT DATA AND POPULATION AT RISK
1. Ambient Nitrosamine Levels Reported
At the present time, there is only isolated data on
ambient * levels of nitrosamines in the environment. The primary reason
is lack of instrumentation, until recently, with sufficient sensitivity
to detect the low levels (ppt) at which nitrosamines are usually
present in the environment. See Section II.C. for a discussion of
measurement technology.
a. In Air
The first reports of ambient data on atmospheric
nitrosamines in the United States were those by Fine in 1975 (95,135).
3
He reported dimethylnitrosamine levels of 0.033-0.96 p.g/m in Balti-
3
more, Maryland and 0.014-0.051 (ig/m in Bella, West Virginia. Nitro-
samines were not detected near Wilmington, Delaware, in Philadelphia,
Pennsylvania, nor in Waltham, Massachusetts. These reports generated
much debate over Fine's analytical techniques (136,137).
63
-------
Fine's original findings were confirmed when he repeated the
sampling of Baltimore air and again detected nitrosamines. They
were also detected independently by Pellizzari in samples that were
collected on the same days and analyzed by a different technique (138).
The nitrosamine levels reported by the two investigators were essen-
tially the same. See Table XI for a compilation of the data.
Dr. Pellizzari conducted additional sampling and analysis
around the FMC facilities during the month of November 1975 and again
detected DMN in the ambient air. These data are also compiled in
Table XI. From the reported atmospheric concentrations of DMN, it is
apparent that a source of DMN exists in this vicinity. Whether this
is solely attributable to emissions from the FMC plant is not clear;
however, it has been established that FMC does contribute to the very
high levels of atmospheric nitrosamines detected. Detection, by EPA,
of lower levels of DMN at Belle, West Virginia, the location of an
amine plant, confirms the supposition that the high levels found in
Baltimore are due to a primary source, the FMC plant.
Dr. Fine has developed a mobile monitoring van which makes real-
time measurements possible. Spot checks for nitrosamines in the air
are now possible in a short period of time. A check for atmospheric
3
nitrosamines in New York revealed a level of 0.8 |ig/m for a 3-minute
sample (141) .
Additional reports of atmospheric nitrosamines were issued in
conjunction with tobacco smoke (142-144). Detected levels of various
64
-------
TABLE XI
AMBIENT NITBOSAMINE LEVELS DETECTED IN AIR
DATE
TIME
LOCATION
CONCENTRATION
INVESTIGATOR
REFERENCE
1975
—
Belle, West
Virginia
0.014-0.051 jig/®3
Fine
95,135
1975
—
FMC plant
Baltimore, Md
0.033-0.96 jig/m*
Fine
95,135
10/14/75
—
IMC plant
Baltimore, Md.
1.3-10.5 p.g/m3
Fine
139
10/14/75
11-2:50 pm
3-6:50 pm
7-10:50 pm
FMC parkint lot
FMC parking lot
FMC parking lot
2133 ng/m3
10,500 + 1,167 ng/m
1,375 + 125 ng/m3
3 Pellizzari
131
10/15/75
11-2:50 pm
3-6:50 pm
11-2:50 pm
3-6:50 pm
FMC parking lot
FMC parking lot
FMC parking lot
FMC parking lot
FMC parking lot
8.7-15 (JLg/m3
416 ng/m3
571 ng/m3
3200 ng/m3
13,437 + 937 ng/m3
Fine
Pellizzari
Pellizzari
Pellizzari
Pellizzari
139
131
131
131
131
10/16/75
10-1:50 am
2-5:50 pm
sewage plant
sewage plant
sewage plant
none
trace
trace
Fine
Pellizzari
Pellizzari
139
131
131
10/17/75
am
am
late pm
9:56-1:46 pm
2:10-6:00 pm
Chessie Pier
Chessie Pier
Chessie Pier
Chessie Pier
Chessie Pier
1.8 (j.g/m3
1.2 |j.g/m
0.13 jig/m3
909 ng/m3
84 ng/m3
Fine
Fine
Fine
Pellizzari
Pellizzari
139
139
139
131
131
10/17/75
—
Bar
1.0-1.2 ng/m3
Fine
139
-------
TABLE XI(CONCLUDED)
DATE
TIME LOCATION CONCENTRATION INVESTIGATOR REFERENCE
11/19/75
2-4:00 pm WNW of dimazine 32 + 1.5 fig/m^ Pellizzari 131
thermal de-
structur on
FMC property
11/20/75
3:45-5:45 pm Fairfield, 200 yd. 1.95 ^ig/m"* Pellizzari 131
from residential
area, Conoco
parking lot
8:20-10:20 pm Merimac Corp., N 1,36 + 0.51 ^*g/m Pellizzari 131
of FMC plant
11/24/75
11:50-1:50 pm FMC lot, SW of 20 + (jig/m^ Pellizzari 131
dimazine plant „
1:55—3:55 pm FMC lot, SW of 14 + 0.2 |ig/m Pellizzari 131
dimazine plant -
6:35-8:35 pm FMC lot, SW of 26 +0.5 pg/® Pellizzari 131
dimazine plant
11/25/75
3
1:48-3:48 pm Northbridge and 7.6 fjg/m Pellizzari 131
Cannery St.,
downwind of FMC
—
3
1973 Factory in Germany 0.04 jjg/m Bretschneider & 140
Matz
12/75
Belle, West Virginia 0.98 |jig/m3 Pellizzari 131
near a suspected
primary source on
the plant premises
-------
nitrosamines have ranged from 0 to 0.137 (j.g per cigarette. One of these
reports has, however, been discredited (143) .
One other reported source of nitrosamines in air is the expired
air of rats that were fed amines and nitrates (145). Presence of
nitrosamines in the expired air is indicative of in^ vivo formation of
nitrosamines in the stomach. The extent of nitrosamine formation in
the stomach is unknown at present; nevertheless, it is interesting
that this process can result in the emission of nitrosamines to the
atmosphere.
Two nitrosamines were detected on the outside surface of the
Surveyor III television camera that was recovered from the moon by
the Apollo 12 astronauts (146) . The source of these compounds was
considered to be the Surveyor III engine exhaust and the lunar module
exhaust because the fuels used could be partially oxidized into the
two nitrosamines. It is, therefore, quite possible that rocket
launchings are contributing nitrosamines to the atmosphere.
Nitrosamine analysis of automobile exhaust was reported with no
identification of the compounds at a detection limit of 25 ppb. Do-
mestic and foreign cars using leaded and unleaded fuel with and with-
out additives were examined by gas chromatography with a Coulson
electrolytic cell (147).
b. In Water
Nitrosamines were detected in water in the United
States by Fine (98 ,135) . Fine analyzed samples of Mississippi River
67
-------
water collected at New Orleans, Louisiana as well as samples from
three water plants in Louisiana. The nitrosamines were not identified,
but the several nitrosamine peaks corresponded to concentrations of
about 0.1 ppb or less. Unidentified peaks corresponding to nitrosamines
at a concentration of 0.1 to 1.0 ng/1 were detected in water around the
FMC plant in Baltimore, Maryland.
Nitrosamines were not detected in any of numerous well water
samples that were analyzed at a detection limit of 1 ppb (124). Dure
et al. (148) reported nitrosamine levels were less than 0.1 (j.g/1 in
samples from the Munich clarification plant and from sediments in
Stamberger Lake and Main River, as 100 ng/1 was the limit of detection
and no peaks corresponding to nitrosamines were observed.
Recent analysis by EPA and Dr. Fine of offshore water samples
from Stone House Cove allowed the conclusion that nitrosamine concen-
trations increase with water depth. This is explained by a tendency
of the nitrosamines in shallow water to either volatilize or photo-
degrade . Sampling in the Kanawha River valley in West Virginia re-
vealed DMN concentrations of 0.3 to 0.7 ppb, with levels of 1 to 5 ppb
found in the waste water from industry along the river.
2. Resultant Exposed Population
Those individuals employed in facilities where carcino-
genic nitrosamines are manufactured, used, or generated are at risk
of exposure. In addition to those few mentioned in Section E.I.,
this would include workers in laboratories where samples are analyzed
68
-------
for nitrosamines, and animal attendents and other employees in
laboratories where experiments involving nitrosamines are being con-
ducted or in laboratories where tobacco smoke is generated.
The general population may be exposed to atmospheric nitrosamines
emitted from coke ovens, petroleum refineries, etc. (see Section E).
However, the involved risk is uncertain at this time and requires
further evaluation. It is also probable that rocket launch pads are
sites of high nitrosamine concentrations during and after rocket
launches, and any personnel present at such times would, therefore,
be exposed.
Nitrosamine exposure due to de novo formation in food (e.g.,
bacon) and water is quite likely as well as exposure due to secondary
formation, which is most likely to occur in polluted areas where
there are high concentrations of both amines and N0x gases. It can
be established that there are areas which have amine production
3*
facilities and also have annual NO2 concentrations of over 100 (J.g/m
As stated previously, individuals residing in these areas may be
risking exposure to nitrosamines.
Tobacco smoke constitutes another population exposure risk. The
effects of smoking on the smoker have been extensively studied but
only recently have the effects of tobacco smoke on the involuntary
smoker (that is, the nonsmoker exposed to tobacco smoke) received
*The Code of Federal Regulations, Appendix A, Section 50.11, establishes
this level as the maximum detectable for an area to remain within air
quality standards.
69
-------
attention. In 1972, the Health Consequences of Smoking, published
by the U.S. Department of Health, Education and Welfare, reviewed the
effects of public exposure to tobacco smoke. The primary constituents
of tobacco smoke that have been investigated are nicotine and carbon
monoxide. Atmospheric emissions of these components from tobacco
smoke differ in that nicotine tends to settle out of the air with or
without ventilation, while the CO level will remain constant until
removal via ventilation occurs (149).
The ambient nitrosamine emissions resulting from tobacco smoke
have not been calculated, however, the total quantity of three nitro-
samines contained in cigarettes has been reported. The mainstream
smoke of an 85 mm U.S. blended cigarette without a filter tip was
found to contain 84 ng nitrosodimethylamine, 30 ng nitrosomethylethyl-
amine, 137 ng nitrosonornicotine, and traces of nitrosodiethylamine
(<5 ng/cigarettes) (143).
To evaluate the risk of nitrosamine exposure to the involuntary
smoker, assume that six individuals, five smokers and one nonsmoker,
occupy a non-ventilated room with dimensions of 8 feet by 12 feet by
3
15 feet (40.776 m ). All five smokers ignite non-filtered cigarettes
and allow them to smoulder, without actively inhaling any smoke, until
they burn completely. Additionally assuming no degradation of the
smoke components, a maximum level of 3.38 ppt nitrosodimethylamine,
1.2 ppt methylethylnitrosamine, 2.31 ppt nitrosonornicotine, and
traces of nitrosodiethylamine would accumulate. The level of
70
-------
nitrosodimethylamine obtained by this method is tenfold lower than
the lowest level of 0.033 ppb detected in the atmospheric samples from
Baltimore. This source of nitrosamines most likely represents a less
significant method of exposure to the general population than the
source in Baltimore; however, it does contribute to the environmental
load of nitrosamines.
In considering the body burden of nitrosamines that could accumu-
late in a smoker, it if were assumed that no compound degradation occurs,
calculation can be made of the total nitrosamines accrued over a period
of time. If one 20-cigarette pack were consumed per day, and if all of
the nitrosamine-containing smoke were inhaled, the total calculable
level introduced to the body each day would be 1,680 ng nitrosodimethyl-
amine, 600 ng nitrosomethylethylamine, 2,740 ng nitrosonornicotine,
and <100 ng nitrosodiethylamine. After a period of one year, once
again assuming no compound degradation, 0.6132 mg of nitrosodimethyl-
amine, 0.219 mg of nitrosomethylethylamine, 1.0 mg of nitrosonornicotine,
and less than 0.0365 mg of nitrosodiethylamine would be present in
the body.
The actual exposure to the smoker quite probably is less than
these figures, as it is uncommon for a cigarette to be completely
inhaled. However, these calculations do estimate an upper limit
which may be significant.
71
-------
E. SOURCES
1. Production and Use
Data from producers of nitrosamines consist primarily of
statistics for the production of the non-carcinogenic N-nitrosodi-
phenylamine, which is used as a retardant in the production of rubber,
since this is the only nitrosamine produced in appreciable quantity.
Apparently, the synthesis of nitrosamines, although potentially hazard-
ous, is simple enough that the scientific community is readily able
to produce sufficient amounts for toxicological and carcinogenic
evaluations without relying on commercial production.
The production of dimethylnitrosamine (DMN) reportedly had ceased
by September 1973. This cessation was precipitated due to the release
by the Occupational Safety and Health Administration of a final en-
vironmental impact study on 14 carcinogens, of which DMN was one of
the listed compounds (23).
DMN, one of the most carcinogenic nitrosamines, has been used as
an intermediate in the production of 1,1-dimethylhydrazine (24). It
is used at this time by the FMC Corporation, a Baltimore hydrazine
production facility, in the production of hypergolic rocket fuel for
the United States Air Force. The Raschig synthesis, which proceeds with
the non-carcinogenic dimethylamine and chloramine, has reportedly been
used successfully in the production of dimethylhydrazine (25) . However,
FMC has a patent on the nitrosamine synthesis and has been utilizing
it rather than the previously mentioned Raschig method. A schematic
72
-------
diagram of the process can be found in Figure 6. Additionally, FMC
employs nitroso-hexamethyleneimine in another in-plant synthetic
process.
Of the numerous nitrosamines that have been synthesized, only one,
nitrosodiphenylamine, has been found to be produced in a quantity
greater than 1000 pounds of $1000 per year. Aldrich Chemicals in
Milwaukee, Wisconsin produces N-methyl-N'-nitroso-N-nitrosoguanidine
and its ethyl and butyl analogs (26) . The analogs are produced in
quantities smaller than MNNG, which is synthesized in less than 100
kilogram amounts. These nitrosamines are sold primarily to government
and scientific research organizations. Eastman Organic Chemicals,
located in Rochester, New York, also produces kilogram quantities of
several nitrosamines for sale to the scientific community. At one
time, Fisher Scientific Company, Pittsburgh, Pennsylvania; J. T. Baker
Laboratory and Chemical Products, Phillipsburg, New Jersey; and K & K
Laboratories, Inc., Plainview, New York, repackaged and/or resold
small quantities obtained from Aldrich and Eastman. At this time,
however, none of the three companies retail nitrosamines.
Nitrosamines have been patented for use, but are no longer utilized,
as gasoline and lubricant additives, pesticides, and antioxidants.
They have also been utilized in the past as fungicides, nematocides,
inhibitors of soil nitrofication, plasticizers, for acrylonitrile
polymers, synthetic intermediates, and as industrial solvents in the
plastic and fiber Industries. Two compounds, di-n-butyl-nitrosamine
73
-------
DIMETHYLAMINE HYDROGEN
AMMONIA
PURIFIED
DMNA
UDMH
DMNA
CITRIC OXIDE
AIR
HYDROGEN-
ATION
DMNA
OXIDATION
AMMONIA
PURIFICATION
DMNA
Source: Devised during private discussion with FMC representatives
on November 11, 1975.
FIGURE 6
BLOCK DIAGRAM OF DIMAZINE PROCESS
-------
and dimethylnitrosamine, can be used as intermediates in the production
of their respective hydrazines. Nitrosamines have been used in con-
densers to increase the dielectric constant and as softeners for co-
polymers . At the present time, nitrosamines appear to be restricted
to usage in the rubber industry, as a retardant, and by the scientific
community (39 ,40,24 ,25) .
Additional possible sources of atmospheric nitrosamines include
emissions from coking and petroleum refineries (150). It has not
been conclusively established that nitrosamines are emitted from these
processes but, based on theoretical chemical reactions, it is suspected.
Contribution to the atmospheric nitrosamine burden may occur via
volatilization of nitrosamines from water and soil. This could occur
after the deposition of these compounds from industrial sources or
subsequent to (te novo formation in the water or in moisture in the
soil.
Due to the possible formation of nitrosamines from amines and
certain nitrogen compounds, a compilation of amines production com-
panies can be found in Table XII (Figure 7 is a map illustrating the
location of these amine production facilities) . The quantity of some
of the compounds produced in the United States is compiled in Table
XIII.
All of the companies listed in Table XII were contacted in an
effort to procure data from each concerning quantity of production.
At this time, only three of the responding companies have made pro-
duction figures available . These were:
75
-------
TABLE XII
U. S. PRODUCERS OF AMINES
ACCTO CHEMICAL COMPANY
JEFFERSON CHEMICAL COMPANY
CHARLESTADT, NEW JERSEY
AUSTIN, TEXAS
CONROE, TEXAS
AIR PRODUCTS & CHEMICALS, INC.
PORT NECHES, TEXAS
PENSACOLA, FLORIDA
MILES LABORATORY
ALDRICH CHEMICAL COMPANY
ELKHART, INDIANA
MILWAUKEE, WISCONSIN
MILLMASTER ONYX CORPORATION
AMES LABS
JERSEY CITY, NEW JERSEY
MILFORD, CONNECTICUT
MOBIL OIL CORPORATION
CELANESE CORPORATION
BEAUMONT, TEXAS
BAY CITY, TEXAS
MONSANTO
COMMERCIAL SOLVENTS CORPORATION
LULING, LOUISIANA
TERRA HAUTE, INDIANA
NALCO CHEMICAL COMPANY
DOW
CHICAGO, ILLINOIS
FREEPORT, TEXAS
NEASE CHEMICAL CORPORATION
DUPONT
STATE COLLEGE, PENNSYLVANIA
BELLE, WEST VIRGINIA
HOUSTON, TEXAS
PENNWALT CORPORATION
WYANDOTTE, MICHIGAN
EASTMAN KODAK COMPANY
KINGSPORT, TENNESSEE
PIERCE CHEMICALS, INC.
ROCHESTER, NEW YORK
ROCKFORD, ILLINOIS
EL PASO PRODUCTS
R.S.A. CORPORATION
ODESSA, TEXAS
ARDSLEY, NEW YORK
ELI LILLY & COMPANY, INC.
REILLEY TAR & CHEMICAL CORP.
LAFAYETTE, INDIANA
INDIANAPOLIS, INDIANA
GAF CORPORATION
ROHM & HAAS
CALVERT CITY, KENTUCKY
PHILADELPHIA, PENNSYLVANIA
LINDEN, NEW JERSEY
DEERPARK, TEXAS
RENSSELAER, NEW JERSEY
SHELL CHEMICAL COMPANY .
HILTON-DAVIS CHEMICAL COMPANY
MARTINEZ, CALIFORNIA
CINCINNATI, OHIO
76
-------
TABLE XII (Concluded)
STAUFFER CHEMICAL COMPANY
UNIROYAL
EDISON, NEW JERSEY
NAUGATUCK, CONNECTICUT
STERLING DRUG COMPANY
VIRGINIA CHEMICALS
CINCINNATI, OHIO
PORTSMOUTH, VIRGINIA
UNION CARBIDE CORPORATION
WARNER LAMBERT
INSTITUTE, WEST VIRGINIA
HOLLAND, MICHIGAN
SOUTH CHARLESTON, WEST
VIRGINIA
TAFT, LOUISIANA
TEXAS CITY, TEXAS
Source: Chemical Information Services, 1975. 1975 Directory of
Chemical Producers United State9 of America. Stanford
Research Institute, Menlo Park, California.
77
-------
F
amine
F!GpUB007UCt'°N
-------
TABLE XIII
AMINE PRODUCTION FOR 1972
AMINE
TONNAGE (104)
DIETHANOLAMINE
4.7
hexamethyleneamine
30.65
N-(1,4-DIMETHYLPENTYL)-N'-
PHENTL-P-PHENYLENEDIAMINE
1.0
ANILINE
19.9
TRIETHANOLAMINE
4.15
ETHANOLAMINE
11.0
DIMETHYLAMINE
4.75
DIARYLARYLENEDIAMINES, MIXED
1.0
HEXAMETHYLENETETRAMINE
4.75
MELAMINE
3.4
ETHYLENE DIAMINE
3.1
TOLUENE, 2,4-DIAMINE
6.65
MONOMETHYLAMINE
1.65
TRIMETHYLAMINE
1.4
DIPROPYLAMINE
1.35
DI-N-BUTYLAMINE
0.19
DIETHYLAMINE
0.55
ALL OTHER ETHYLAMINES
2.2
TOTAL BUTYLAMINES
0.95
Source: Chemical Information Services, 1975. 1975 Directory of
Chemical Producers United States of America. Stanford
Research Institute, Menlo Park, California.
79
-------
1. Aidrich Chemical Company, Inc.
90-175 kg dl-a-methylbenzylamine synthesized each year for
the last five years.
2. Ames Laboratories
20-50 pounds paramethylbanzylamine synthesized each year for
the last five years.
3. Virginia Chemicals, Inc. (1974 figures)
Dipropylamine 11,100,000 lbs.
Tripropylamine 42,000 lbs.
Dibutylamine 1,523,000 lbs.
Tributylamine 150,000 lbs.
Using the 1975 Directory of Chemical Producers, production capacity
for several companies was procured. These are:
1. GAF
10,000 lbs. capacity for mono-, di-, and trimethylamine.
2. EI Dupont
165,000,000 lbs. capacity for mono-, di-, and trimethylamine.
3. Commercial Solvents Corp.
18,000,000 lbs. capacity for mono-, di-, and trimethylamine.
4 . Air Products and Chemicals , Inc .
50,000,000 lbs. capacity for mono-, di-, and trimethylamine.
The formation of amines has been indicated during food cooking
processes as well as through commercial synthesis routes (151) .
Amines are also emitted from coking arid petroleum refineries, sewage
treatment facilities, and during organic decomposition or incineration
(152,153). They have been indicated as possible atmospheric pollutants
produced by solid waste disposal rendering plants and feedlots (152).
80
-------
Amines are also distributed to the environment in the form of drugs
and pesticides. (See Section II.F. for a complete discussion of by-
product emission points in industry.)
In addition to environmental emissions of amines due to either
direct or indirect production of the compounds, dispersive use can
contribute significantly to the environmental load. A compilation
of these uses for 33 synthetically produced amines can be found in
Figure 8. The figures found in Appendix A are keyed to Figure 8 by
number . Utilization of Appendix A figures provides an illustration
of the losses incurred during production or dispersive and consumptive
uses of the specific amines, while Figure 8 affords an overview of
amine emissions to the environment as a group.
The use of amines as intermediates in manufacturing processes
results in losses to air and water. Utilization of the amines in
emulsion paints, as fuel additives and lubricants, cutting oils,
cleaners and polishes, cosmetics, priming agents, protective coatings,
paint removers, dehairing agents, and as a warning agent for natural
gas contributes to the loss of these compounds to the air. Amine
consumption in pesticides, as a wool scouring agent, in shampoos,
as emulsifying agents, and in the desalination of brackish water
increases the amine content of water. Disposal of products manu-
factured from amines also contributes to the environmental burden
via leaching from landfills and dumps containing amine products, and
from incinerator burning and vaporization of these products. The
81
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AVAILABLE
DIGITALLY
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fate of disposed amines is to the soil and water in the first
instance and to the air in the latter case. However, the initial
respository acts only as a holding zone. The amines with low vapor
pressures* can readily transfer from water to atmosphere and those
that are water soluble will recycle to the hydrosphere during inclement
weather. Therefore, as visualized in Figure 8, the intentional
production of amines is only the first step in a chain reaction which
disperses the compounds to the entire ecosphere. However, this
dispersion accounts for only a fraction of production. See Table XIV
for a compilation of some physical properties of representative amines.
Amines are not routinely monitored because hazard to health
and/or defined standards have not yet been determined (155,156).
Because the compounds readily assault the olfactory sense with a
pungent odor, it is well established that some amines can and do
volatilize due to their high vapor pressure and are known to be
present atmospherically (157). A colorimetric test has been developed
for the detection of ambient amines; however, the detection limits
are high (158). Dr. Russell Hendricks, coordinator of the University
of Utah laboratory, which analyzes samples for the National Institute
for Occupational Safety and Health, reported evaluation .in 1974 of
55 samples for the presence of various amines. Of these samples, 32
*As a general rule, those amines containing four or fewer carbon
atoms will volatilize because of characteristically low vapor pres-
sures while the compounds with more than five carbons will not (154).
85
-------
TABLE XIV
PROPERTIES OF REPRESENTATIVE AMINES
Formula
Specific
Melting
Boiling
Vapor Pressure
Amine
Formula
Weight
Gravity
Point,°C
Point,°C
(1mm Hg)
Secondary Amines
Allylaniline
133.09
0.982
209
o-Aminodiphenylamine . . .
184.11.
79
p-Aminodiphenylamine . . .
. . . (4)nh2c6h4nhc6h5
184.11
66
Benzylidene aniline ....
Butylaniline (iso) ....
. . . c6h5nhc4h9
149.13
231
Butylaniline (n)
. . . c6h5nhc4h9
149.13
240.9
Dibenzylamine
197.13
1.026
-26
300
118.3
Dibutylamine (iso)
. . . (c4h9)2nh
129.16
139
Dibutylamine (n)
• • • (c4h9)2nh
129.16
0.767
161
Diethanolamine
105.09
28
270
Diethylaraine
. . . (c2h5)2nh
73.09
0.711
-39
55
*
-33.0
Dime thylamine
45.06
0.680
-96
7
-87.7
Diphenylamine
169.09
1.159
53
302
108.3
Dipropylamine (iso) . . .
. . . (c3h7)2nh
101.13
83
Dipropylamine (n)
101.13
0.738
-40
110
Ethylaniline
- • • C?5mc2»5
121.09
0.963
-63.5
240.7
38.5
Hetfaylaniline
107.08
0.986
-57
195.7
36.0
Methylethylamine
. . . (CHj)(C2H5)NH
59.13
• • • • «
34
Phenylbenzylamine . . . . .
183.11
1.038
37
300
Propylaniline (n)
• • •
135.11
0.949
222
*10 maBg
-------
TABLE XIV (CONCLUDED)
Formula
Specific
Melting
Boiling
Vapor Pressure
Amine
Formula
Weight
Gravity
Point, °C
Point,°C
(1mm Hg)
Tertiary Amines
Dibenzylaniline
. . . c6h5n(ch2c6h5)2
273.16
70
Dibutylaniline (n)
• • • WW 2
205.19
0.907
262.8
Dimethylaniline
. . . c6h5n(ch3)2
121.09
0.956
1.7
193.5
29.5
Dimethylethylamine
. . . (ch3)2nc2h5
73.16
37
Diphenylbenzylamine ....
• • • (C6H5)2NCH2C6H5
259.37
86
Dipropylaniline (iso) . . .
• • • WW2
177.16
Dipropylaniline (n) ....
• • • W(C3H7>2
177.16
0.910
241
Ethyldiphenylamine
. . . c2h5n(c6h5)2
197.13
297
Methyldiethylamine
. . . ch3n(c2h5)2
87.11
65
Methyldiphenylamine ....
• • • CH3N(C6H5)2
183.11
1.047
-7.6
293.4
103.5
Methylethylaniline
. . . (ch3)(c2h5)nc6h5
135.11
201
Tribenzylamine
• • • (C6H5CH2)3N
287.17
0.991
92
385
Tributylanine (iso) . . . .
. • •
-------
were tested for dlmethylaniline, 10 for dimethylamine, 7 for o-naphtha-
lene, and 6 for diethylamide. Results, whether qualitative or quanti-
tative, are not readily available (159,160).
Amines have also been detected and quantitated in water. Lauryl-
amine was identified in trace amounts in a sample from the River Elbe
while Amersbed Brook, a dumping location for industrial effluent,
reportedly contained 10 |ig/kg methylamine, 5 jig/kg dimethylamine, 20
fig/kg ethylamine, and 23 other amines, with concentration variations
of 1 to 3 pg/kg. Methylamine was detected in Timmermoor Swamp at a
level of 2 (Jg/kg along with 25 other amines in concentrations of
0.1 to 0.5 pg/kg (161). In a German publication, it was reported that
dimethylamine, diethylamine, pyrrolidine, piperazine, and NO^ were
detected in all the water samples analyzed excepting tapwater (162) . A
summary of the levels detected and locations of sampling areas is con-
tained in Table XV.
2. Environmental Occurrence and Formation
a. Nitrosamines
Reports have suggested the formation of dimethyInitro-
samine in a wide variety of unprocessed food materials (105) . The
exact origin of the nitrosamine in these instances is not clear. The
wheat plant, wheat grain, and unprocessed milk and cheese have been
reported to contain undetermined quantities of DMN (163) . The pres-
ence of nitrosamines has also been suggested in tobacco and tobacco
smoke, fish meal, wheat kernels, smoked fish, meat, mushrooms, the
fruit of Solanurn incanum, a solanaceous bush, and alcoholic beverages
(24,105,164) .
88
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TABLE XV
LOCATIONS OF SAMPLING AREAS AND CORRESPONDING LEVELS OF AMINES AND N02 DETECTED
Sample Amines Detected*
Concentration Detected
N0„ Concentration
Detected
Tapwater
Water from
the Anmer River
MA
0.7
ppb
0.9 mb/1
DEA
1.6
ppb
PYRR
1.0
ppb
PIP
0.5
ppb
Water from
the Neckar River
DMA
0.5
ppb
0.18 mb/1
DEA
1.7
ppb
PYRR
0.3
ppb
PI*
0.2
PPb
Lake water
from Stein
DMA
0.7
ppb
1.1 mg/1
DEA
1.2
ppb
PYRR
0.4
ppb
Filtration
plant in Reutlingen
DMA
1.0
ppb
0.64 mg/1
DEA
2.1
ppb
PYRR
0.5
ppb
PIP
0.3
ppb
Filtration
plant in Pfullingen
IMA
1.2
ppb
0.83 mg/1
DEA
1.8
ppb
*DMA - Dimethylamine
DEA - Diethylamine
PYRR - Pyrrolidine
PIP - Piperazine
-------
Secondary, or atmospheric, formation from the reaction of nitrites,
nitrates, or NO^ gases with amines, normally secondary amines, is one
widely recognized possible explanation for the environmental appearance
of nitrosamines (see Table I for a compilation of amines that have
been nitrosated to nitrosamines) . Secondary amines react with nitrites
to form nitrosamines under conditions of defined pH and other condi-
tions similar to those in the mammalian stomach and in vitro in gastric
juice (21,24). This de novo formation was substantiated by the
appearance of esophageal tumors, which are induced by nitrosomethyl-
amine, that had been initiated in rats given nitrite and methylbenzyl-
amine, the precursors of the carcinogenic nitrosamine (21). Similar
instances are reported in the literature (165,166). Aminopyrine, a
tertiary amine formerly used as an analgesic in the United States,
caused liver tumors in almost 100 percent of the animals tested, even
at a dose of 250 ppm in water, by forming DMN after nitrosation with
nitrite. In vivo formation of all nitrosamines is not necessarily
possible, as evidenced by the absence of tumors induced by oxytetra-
cycline fed simultaneously with nitrites (60).
Mixtures of NO2 and nitric oxide, the two major environmental
oxides of nitrogen which contribute to the atmospheric burden of nitrous
acid, are capable of nitrosating secondary and tertiary amines to
form the corresponding nitrosamines; however, the efficiency of this
conversion is unknown (167) . Because N0^ gases are known to be readily
absorbed by the body during inhalation, the real possibility of
internal formation of nitrosamines must be Investigated (151).
90
-------
In vivo conversion of nitrosamine precursors to the nitrosamine
is favored when the compound being formed is of low solubility, as
in the case of the cyclic amines (21) . The occurrence of nitrosation
has been implicated during the storage and/or processing of foods (168),
while reactions of nitrites with more than 20 typical widely used
compounds have formed measurable amounts of nitroso compounds within
two hours at body temperature (60) . These chemical tests are being
complemented with animal feeding experiments in which the compound
analyzed and nitrite are administered to rats daily for one year.
The rats are then kept until death, at which time an extensive patho-
logical examination is performed in order to detect possible tumors
induced by nitroso compounds (60).
The in vivo formation of nitrosamines from ingested precursors
is a potential problem and must be further investigated. However,
the mere availability of the nitrites and secondary amines is not
necessarily a hazard since both precursors must be simultaneously
present in the stomach to form the nitrosamine. Even after nitrosamine
formation, if the compound formed is not carcinogenic, there may be
no inherent danger (21).
The possibility of secondary and in_ vivo formation of nitrosamines
is enhanced by the widespread availability of nitrites, nitrates, NO^
gases, and amines. Nitrates and nitrites, at levels of 200 ppm or
less, are used as food additives in the manufacture of cured meat and
fish products (169 ,170) . The addition of these compounds is resultant
91
-------
from their roles as color fixatives, preservatives, and flavor en-
hancers which could effect in vivo formation of nitrosamines. Nitrite
has also been consistently detected in human saliva at concentrations
of 6 to 10 ppm (171) . Utilization of high nitrate content fertilizers
may increase the level of nitrate in water supplies, while plants
grown on deficient soil have been shown to contain nitrites (60). All
of these sources could contribute to the in vivo formation of nitro-
samines .
b. NO
x
The origins of atmospheric NO^ can be traced to two
commonly occurring natural processes, bacterial degradation and slow
reactions of fossil fuels, as well as to anthropogenic sources.
Bacteria are able to decompose the nitrites and nitrates found
in various substances, forming NO, a colorless, odorless gas. This
nitrogen oxide is then further oxidized to NO2 (172) . Natural forma-
tion of nitrogen dioxide due to bacterial production in closed silos
has reportedly resulted in hazardous concentrations of several hundred
ppm (173) . Nitrogen oxides are also formed during combustion as a
result of the oxidation of organic nitrogen compounds in fossil fuels
and by the thermal fixation of atmospheric nitrogen gas. These organic
nitrogen compounds can be found in both coal and oil in concentrations
of 1 to 2 percent by weight in bituminous coal and 0.05 to 0.5 percent
in crude oil (172) . These are sources of nitrosating agents which
could be precursors for secondary formation.
92
-------
NO and NC^, as pollutants, are derived primarily from combustion
processes in which nitrogen is fixed in air and fuel by high tempera-
tures and during which the combustion quenching is rapid enough to
reduce decomposition of the nitrogen oxide back to gaseous nitrogen
and oxygen. NO is the predominant product of this oxidation with
approximately 5 to 40 percent of the nitrogen in coal and 20 to 100 percent
of the nitrogen in oil being oxidized in this manner during combustion.
Subsequent oxidation of the produced NO occurs in the stack gas
or, occasionally, in the diluted plume. Dilution of the NO concentra-
3
tion to 1 ppm (1230 pg/m ) or less reduces the rate of N02 formation
via NO oxidation (174). However, this NO can also rapidly interact
with tropospheric ambient ozone to form N02. It is generally accepted
that these ubiquitous concentrations of 0^ will .continually maintain
an atmospheric predominance of N02 over NO, although higher levels of
NO than NO2 have been detected in some remote locations (175,176).
The natural removal of NO2 from the atmosphere occurs either
by precipitation, continued ozone oxidation to a nitrous salt, or, in
the presence of water, by the more common conversion to HNO^ via HN02.
The nitric acid is subsequently removed from the air by reactions
with NH3 and hydroscopic particle absorption and by rainfall (177).
Estimation of total annual emissions of N0^ gases has been
reported corresponding to fuel usage. According to one source,
Robinson and Tonnins, the 1967 emissions of N02 totaled 52.9 x 10^
tons. Coal combustion accounted for 51 percent of the emissions
93
-------
followed by petroleum production and combustion which contributed 41
percent and the combustion of natural gas with 4 percent. On a local
basis, however, natural gas oxidation could be a major source of ambient
NO dependent upon the fuel usage of the area. Table XVI contains a
compilation of the world wide N02 emissions corresponding to fuel
usage for 1967 (178) .
The emissions resulting from U.S. fuel consumption produce
approximately 50 percent of the global anthropogenic N0^ emissions
(174) . While NO^ emissions directly related to human activities are
far less than the 50 x 10^ tons emitted yearly from natural sources,
the spatial arrangement of urban emissions leads to 10-100 fold greater
NO concentrations than are found in rural environments (174) .
x
In the United States fuel combustion is the major source of
anthropogenic NO^ emissions. Of the estimated 24.6 x 10^ tons of
NO^ emitted domestically in 1972 the combustion of coal, oil, natural
gas and motor vehicle fuel accounted for greater than 85 percent.
Stationary area and point source emissions account for an estimated
64 percent of all the NO . Direct stationary fuel combustion is the
largest source category (49.7 percent), and the utilization of coal
is the largest single contributor to this category (174) .
The largest source of transportation-related N0x is gasoline
powered vehicles,which produce 32 percent of all N0x and 82 percent
of the transportation-related pollutant. The manufacture and use
of nitric acid in addition to petroleum refineries constitute the
94
-------
TABLE XVI
WORLDWIDE EMISSIONS OF NITROGEN DIOXIDE IN 1967
FUEL
SOURCE
N02 EMISSIONS %
TOTAL
(106 Tons)
COAL
51
Power Generation
12.2
23
Industrial
13.7
26
Domestic/Commercial
1.0
2
PETROLEUM
41
Refinery Production
0.7
1
Transportation (gasoline)
7.5
14
Power Generation: Kerosene
1.3
2
Fuel Oil
3.6
7
Residual Oil
9.2
17
NATURAL
GAS
4
Power Generation
0.6
1
Industrial
1.1
2
Domestic/Commercial
0.4
1
OTHER
Incineration
0.5
1
Wood
0.3
1
Forest Fires
0.5
1
TOTAL
52.9
100
Source:
Adapted from Air Quality and Stationary Source Emission
Control, Committee on Public Works
, U.S. Senate, March
1975.
95
-------
largest contributors to industrial NO emissions with the electroplating,
X
welding, engraving and metal clearing industries also emitting
6
significant levels. These processes contributed 2.9 x 10 tons of
NO^ to the environment in 1972, amounting to 11.7 percent of the
total nationwide emissions (174) .
Of the total domestic N0x produced yearly, 77 percent occurs
in highly populated areas due to the presence in these locations of
71 percent of the motor vehicles and 80 percent of the stationary
sources, including power plants, incinerators, and refineries. The
estimated total national NO^ emissions have increased from 6.1 x 10^
tons in 1940 to 24.6 x 10^ tons in 1972. Emissions from motor
vehicles increased steadily from 4.6 to 4.9 percent each year
those from power plants have increased at an annual rate of 6.9 to
7 .4 percent. See Table XVII and Figure 9 for compilations of nation-
wide NO emissions (179) .
x
Reliable concentration data for urban NO and N02 are difficult
to procure as a result of controversy and uncertainty pertaining to
NO^ measurement methodology. However, worldwide detection generally
illustrates N0x concentration variations with latitude, altitude,
and growing season. Dry season NO^ levels have reportedly been four-
fold lower than wet season values, while sea level Averages were
found to be one-third lower than averages detected at 10,000 feet
(180,181). N02 levels in the relatively unpolluted areas of the con-
tinental United States have been found to average in the 4 ppb range,
96
-------
TABLE XVII
NATIONWIDE NO EMISSIONS, 1940-1970
x
Source Category
NO
Emissions
(10^ tons/year)
1940
X"
1950
1960
1968
1969
1970
Stationary Fuel Combustion
3.5
4.3
5.2
9.7
10.2
10.0
Electric Generation
0.6
1.2
2.3
4.2
4.3
4.7
Industrial
1.9
2.0
1.8
3.7
4.6
4.5
Commercial-Institutional
0.1
0.1
0.2
1.0
0.4
0.2
Residential
0.9
1.0
0.9
0.8
0.9
0.6
Industrial Process Losses
0.1
0.1
0.1
0.2
0.2
0.2
Solid Waste Disposal
0.1
0.2
0.2
0.2
0.4
0.4
Transportation
1.7
2.9
4.3
7.5
8.3
8.8
Road Vehicles
1.4
2.2
3.5
5.5
5.8
6.2
Gasoline
1.4
2.15
3.2
4.8
5.1
5.4
Diesel
0.1
0.05
0.3
0.7
0.7
0.8
Other
0.3
0.7
0.8
2.0
2.5
2.6
Miscellaneous
0.8
0.4
0.2
0.2
0.2
0.1
Total
6.1
7.9
10.0
18.2
19.3
19.5
Source: Air Quality and Stationary Source Emission Control, Committee on Public Works, U.S.
Senate, March 1975.
-------
25
20
Total emissions
Stationary fuel combustion
Road vehicles
Electricity generation
Industrial fuel combustion
Industrial process loss
15
o
t-H
10
1970 1972
1940
1960
1968
1950
1969
YEAR
Source: Air Quality and Stationary Source Emission Control,
Committee on Public Works, U.S. Senate, March 1975.
FIGURE 8
NATIONWIDE NOx EMISSION TRENDS 1940-1972
-------
while NO concentrations averaged only 2 ppb (181,182). However, NO
has varied from 0.1 to 0.5 ppm, while NO£ fluctuated from 0.05 to
0.3 ppm in Los Angeles smog (176,183).
All of these data affirm the widespread availability of gaseous
NO^, which may play a significant role furing atmospheric nitrosation
of amines to nitrosamines.
3 . Formation as a Degradation Product of a More Complex
Compound
Nitrilotriacetic acid (NTA) , which can be produced from
formaldehyde, ammonia, and hydrogen cyanide, forms water-soluble com-
plexes with calcium and magnesium at pH 10, the pH of washing water.
This factor made it a useful component in detergents. A further
positive characteristic is that these complexes are reportedly not
stable at pH 7, the normal pH of surface water; therefore, the
chelating effect would not increase the metallic content of public
waters. These factors, coupled with the non-toxic characteristics
of NTA, made it at one time a desirable candidate for use as a sub-
stitute for sodium tripolyphosphate (184).
The sodium salt of NTA, or NTA itself, is used as a chelating
agent for the prevention of scale in the cooling system of power
plants. Ethylenediamine tetraacetic acid (EDTA) is more frequently
used in this capacity as it is stronger' and more reactive; however,
NTA is fairly commonly utilized (185) .
The possibility of degradation of NTA, a tertiary amine, into
secondary and primary amines with the subsequent nitrosation of these
99 i
-------
amines by nitrites to form carcinogenic nitrosamines has been sug-
gested (186), however, the data are incolclusive. Epstein proposed the
formation of iminodiacetic acid and sarcosine, both secondary amines,
from NTA by the process of carbon fragment loss. By reaction with
nitrous acid, these compounds form N-nitroso-iminodiacetic acid and
N-nitrososarcosine, respectively (187). Nitrosocarcosine is a known
carcinogen in rats, while the carcinogenicity of nitrosoiminodiacetic
acid is unknown (184). The formation of nitrosamines, after NTA de-
gradation, was indicated as a fact in another publication, strength-
ening Epstein's proposal (166). Evidence was purported in another
study for the biodegradation of NTA by river water microorganisms, which
was so efficient that none of the amino acids possible from this
enzymatic metabolism were detectable at a level of 0.025 mg/1 (184).
If this is correct, then the formation of nitrosamines from NTA would
not be probable. For the United States, this question is not di-
rectly applicable, since NTA was voluntarily banned as a substitute
for phosphates approximately five years ago. NTA does have other
applications that are utilized in the United States. In 1974, the
total U.S. consumption of the trisodium salt of NTA was 13 million
pounds. Of this, 100 percent was utilized as a chelating agent in
textile processing, power plants, pharmaceuticals, synthetic rubber
production, and tanning (184). The contribution of this consumed NTA
to the NTA content of surface waters has not been evaluated. However,
the possibility of nitrosamine formation during the degradation of the
NTA should be further investigated.
100
-------
Residual dimethylnitrosamine was detected in a solvent washing
of the Surveyor III camera which, prior to recovery by the Apollo 12
mission, had been on the moon for 31 months (146). This partial oxi-
dation product of the unsymmetrical dimethylhydrazine (UDMH), which
was used in the lunar module fuel, may have been a component of the
rocket exhaust deposited on the camera. Alternatively, the DMN,
which is present in the UDMH at a level of 0.12 percent, may have
been deposited at some time before combustion due to a system malfunc-
tion. Methyl oxazine, another nitrosamine, was also detected and
attributed to incomplete combustion of the monomethylhydrazine, which
was the primary constituent of the Surveyor III rocket fuel (146) .
F. CONTROL METHODOLOGY
The control of emission of nitrogenous compounds to the
atmosphere from gaseous effluents can be based on one of three
fundamental processes-absorption, adsorption, or chemical change.
The first two processes remove the compound from the air stream
unaltered and, thus, it can be retrieved for recycling or destruction.
Should the compound be left on the absorbent or adsorbent, control
will not have been achieved-the process will merely effect the
transfer of the compound from one medium to another. Chemical
change will result in the destruction of the compound and its removal
from the environment.
Absorption in a liquid of specific components of a gas stream is
effected by wet scrubbing. The gas stream is passed through a column
101
-------
or tower while the liquid flows through in countercurrent flow. The
column is usually packed in order to provide a greater surface area
for the interaction of liquid and gas. The packing material may be
metal, glass, ceramic, plastic, wood, carbon, or even rock or stone.
It may be broken pieces or in specific shapes—e.g., rings (Raschig,
Lessing, Pall, or Dixon rings), saddles (Berl, Intalox, or McMahon
saddles), grids, slats, and mesh. The packing may be randomly distri-
buted or carefully stacked. The gas stream enters the vertical column
at the bottom, the liquid at the top. As the liquid trickles over the
packing, it absorbs the nitrogenous compounds from the gas. The
cleansed gas (lean gas) exits from the top of the column; the liquid
with the absorbed compounds is drained from the bottom of the column
(188). The absorbed compounds can then be reclaimed (e.g, by distil-
lation) and recycled. Alternatively, the drained liquid can be incin-
erated (see below for discussion of combustion) or otherwise treated
in order to effect degradation or decomposition of the absorbed
compound(s).
Theoretically, adsorption onto a solid surface of specific com-
ponents of a gas stream is effected by passage of the gas through the
adsorbent. This hypothetical adsorption capacity depends on the
surface area, pore volume, and mean pore diameter of the adsorbent as
well as on the chemical properties (polarity) of the solid and of the
gas. Thus, activated carbon, a non-polar solid, is very effective as
an adsorbent of non-polar organic molecules; the polar adsorbents
102
-------
(silica oxides, metallic oxides, synthetic zeolites) adsorb polar
molecules (e.g., ammonia) preferentially (188). As with the absorbed
compounds, the ultimate fate of the adsorbed compounds determines
whether they are effectively removed from the environment. Regenera-
tion of activated carbon, for example, removes the adsorbates from
the adsorbent (189) . This can be effected in various ways (190) .
Some activated carbon systems are regenerable in situ, others are not.
Regeneration can be effected by superheated steam (at about 50°F hotter
than the boiling point of adsorbed substance) ; in this procedure, the
adsorbed compound is removed by steam distillation and it can then be
condensed and recovered. Alternatively, the adsorbate can be removed
by solvent wash and then recovered by distillation and condensation;
when this procedure is used, the carbon is reactivated with steam.
A combination adsorption-incineration system is useful for air streams
with low concentrations of pollutants; the hot gas stream used for
regeneration of the carbon removes the adsorbed material and it then
passes into the incinerator. This method provides much more economical
incineration because the carbon concentrates the adsorbed substances
prior to incineration. Calgon thermally reactivates spent carbon at
about 1800°F; this effectively incinerates adsorbed nitrogenous com-
pounds. On the other hand, instead of being regenerated, the spent
carbon can be thrown away. If it is buried in a landfill, the nitro-
genous compounds are merely transferred from the atmsophere to the
lithosphere. An alternative method of disposal is use of the spent
carbon with the adsorbed compounds as fuel in a coal-fired boiler.
103
-------
The most common method for effecting chemical change of nitro-
genous compounds is combustion by incineration. Combustion produces
the NO^ gases, with the particular state of oxidation being a function
of the completeness of combustion. The other products of combustion
of organic nitrogenous compounds are carbon dioxide and water. Ade-
quate oxygen must be present to ensure complete oxidation; oxygen
is usually present in excess (15-20%) of the stoichiometric quantity
for conventional combustion processes, whereas the use of catalysts
(e.g., palladium supported on activated alumina, platinum on high
nickel alloy media, platinum and alumina on procelain) can eliminate
the requirement for excess oxygen. Another specification for combus-
tion is proper temperature; especially high temperatures might be
required for the destruction of some specific compounds, including
nitrosamines, amines, and ammonia. Temperature in the combustion
chamber is usually maintained at 900° to 1600°F (482° to 871°C) . Com-
bustion can occur in open flares or in enclosed combustion chambers
(188) . Combustion under proper conditions is an effective means of
degrading nitrosamines.
1. Nitrosamines
Nitrosamines are used in a manufacturing process in
significant quantities only at the FMC Corporation plant in Baltimore,
Maryland. The nitrosamines serve as an intermediate in the production
of unsymmetrical 1,1-dimethyl-hydrazine. Gas streams in the plant are
water-scrubbed, and the water is then destructed in a thermal
104
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decomposer by an incineration process at about 1500°F (188). Scrubbing
and incineration of all gas streams would effect control of nitrosamine
emissions to air. There is reportedly zero discharge of nitrosamines
to waterways (191) .
Some waste that contains nitrosamines is generated by the pro-
duction process. This waste could contribute nitrosamines to the
environment if it were not disposed of properly. It is unclear whether
there is an appropriate method of disposal—that is , one which is
suitable and practicable as well as feasible. A request for a permit
for ocean dumping of the waste was denied (192). Use of ultraviolet
irradiation to decompose the nitrosamines in the waste prior to ocean
dumping was considered too expensive. The waste is, therefore, being
held in storage tanks at the plant (192).
According to Col. William Mabson, USAF, the only waste that is
not presently destroyed in the FMC plant thermal destructor is the
material containing sodium, as the sodium reacts with silica in the
firebrick of the incinerator, which would cause disintegration of the
interior of the structure. All other non-sodium material is combusted
in the thermal destructor. This includes the rainwater runoff from
the pad itself, if no sodium is present. The material that does con-
tain sodium is stored in diked tanks, lined with impermeable membranes,
and fitted with charcoal filters in the vents, at the GSA tank farm
in Somerville, New Jersey (193 ,194) .
105
-------
Good housekeeping practices (e.g., limitation of spills, prompt
location and correction of leaks) and use of closed systems wherever
possible will minimize worker exposure to nitrosamines as well as
nitrosamine emissions from the plant. Wet scrubbing followed by
incineration can effectively limit nitrosamine emissions from the
plant to the atmosphere. This procedure may contribute to the NO^
gases present in the atmosphere; nevertheless, at present, combustion
is the only appropriate method for effecting degradation of the nitro-
samine compound. Photolysis does effect nitrosamine decomposition
(46,192); however, the practicality and economic feasibility of using
ultraviolet irradiation on a commercial scale have not been demonstrated.
2. Precursors
Inasmuch as some of the nitrosamine present in the
atmosphere may be attributable to secondary formation, primarily from
the direct reaction of amines with N0x, all sources of these nitrogen
compounds should be considered in the planning of control strategies.
Nitrogenous compounds in the atmosphere include amines, nitrogen
oxides, and nitrates/nitrites. One might speculate that there are
sufficient quantities of these compounds, and their elemental con-
stituents or precursors, naturally present in air to allow secondary
formation of nitrosamines. Nevertheless, anthropogenic contribution
to their presence in the atmosphere should be considered in order to
deduce what controls can be applied to which sources in order to limit
these emissions.
106
-------
Amines
Amines originate from many sources, some attributable to man and
some natural. Of the former, some are subject to emission control
whereas others are not. Controls are not applicable to amine emissions
from natural sources.
In this section, methodology for the control of amine emissions
is discussed in terms of the source of the amines—that is, manufacture,
industrial use, coking and petroleum refining, incineration and com-
bustion, sewage treatment, natural sources, pesticides, and drugs.
• Manufacture. Amines are manufactured in at least 40 plants
throughout the United States (see Table XII) and these plants constitute
specific sources of amine emissions to air. In reality, production
losses are probably quite low because manufacturers minimize losses in
order to maximize production. Furthermore, many amines are pungent
and their odor thresholds are very low (e.g., monomethylamine » 20 ppb;
dimethylamine « 23.2 or 47 ppb, according to differing reports;
trimethylamine ¦ 0.2 ppb; allylamine ¦ 28 ppm) (195); consequently,
companies must minimize amine emissions in order to maintain good
relations with the communities in which they are located.
Figures 10 and 11 diagram the synthesis processes for one amine,
melamine, as well as three types of amines—¦methylamines, ethanolamines,
and alkylamines. (The processes are the only ones found, with
schematic diagrams, that are not considered proprietary information
[196,197].) The hatching indicates the steps in the processes where
107
-------
RECYCLE NH AND AMINES
CATALYTIC
DMA
COLUMN
MMA
COLUMN
TMA
COLUMN
METHANOL
NH,
WASTE
HEATER
VENT
' kH, AND CO^ ^
METHYUMINES FROM AMMONIA AND METHANOL
WATER RECYCLE
ABSORBER
MEA
MULTIPLE
COLUMN
STRIPPER
COLUMN
REACTOR
SYSTEM
HEATER
TEA
ETHYLENE OXIDE
RECYCLE AMINE!
ETHAMOLAMINES FROM AMMONIA AMD ETHYLENE OXIDE
PRECOOLER
COOLER
HOT-GAS
SEPARATOR
CATALYTIC
FLUIDIZED-I
REACTOR
MELAMINE
BYPRODUCTS & CATALYST FINES
COMPRESSOR
RECOVERED URSA
MELAMINE FROM UREA
Austin, C.T., "Th« Industrially Significant Organic Ch*aical»," ty/A POSSIBLE SITES
Chen. Ena.. 86-90, April 1974 and 149-156, June 1974. wyA • 0f EMISSIONS
FIGURE 10. SCHEMATICS FOR SYNTHESIS OF METHYLAMINES, ETHANOUMME8. AND MELAMINE
108
-------
Separator
Vaporizers Reactor \ Hydrogen
o
SO
Sh
Alcohol
m
Recycle compressor
215
Make up
Hydrogen
Hydrogen Ammonia
l—mz column
tail gases / Monoamine
column
tn
J7
Diamine
column
4-
Triamine
Recycle
T
/
IJ
>?}//,
Triamine
~
Diamine
~
Monoamine
~
SOURCE: Adapted from Hahn, E.V. The Petrochemical Industry:
Markets and Economics, McGraw-Hill Company, New York, 1970.
FIGURE 11
SCHEMATIC SYNTHESIS OF ALKYLAMINES
-------
amines might be lost to the environment. In the synthesis of methyl-
amines and alkylamines, there is venting of gases and also discharge
of liquid waste. Ethanolamine synthesis entails the use of a complete-
ly closed system. Gaseous by-products can be vented during the syn-
thesis of melamine.
A closed system should be used wherever possible for handling the
amines during manufacture, loading, and shipment, and amines should
be removed from all effluents before they are discharged into a water-
way or into the atmosphere. Wet scrubbing is the most effective
method for removing amines from the gaseous effluents. The liquid
from the scrubber as well as the liquid effluents can be distilled
for amine recovery or incinerated in order to effect amine destruc-
tion. Alternatively, activated carbon vapor (or liquid) phase adsorp-
tion systems can be used; regeneration of the carbon adsorbent results
in desorption of the amines for subsequent recycling or incineration.
The controls being used in DuPont amine-producing plants located
in Belle, West Virginia and Houston, Texas (198) illustrate the
procedures which can be instituted to effect control of amine emissions
to the environment. Aqueous effluents are passed through a stripping
column and organics and water are then distilled off the top in a
50:50 mixture which, depending on its quality, is either burned or
recycled. Gaseous elements (derived in processing, sampling, etc.)
are run through a column packed with Pall rings; when chilled water is
circulated in the column, 99.995 percent of the amines are absorbed
110
-------
by the water and recovered for recycling, whereas the inert gases
(N^ , CO, H^) and remaining amines, totaling 1.3 to 2.7 ppm, pass
through the column (198). Incineration by flaring, which also destroys
any amines that may be present in the plant atmosphere (usually be-
cause of a production upset), is being considered as a backup system
(198). When there are any shutdowns, such as for maintenance, the
equipment is flushed with water and the amines are recovered by dis-
tillation. Good housekeeping practices also control amine emissions;
these include such things as using the best gaskets available, keeping
flanges tightened, locating and correcting leaks promptly (most leaks
are signaled by the strong amine odor), checking for minute leaks at
the start of every shift through use of an SC^ bomb (SC>2 plus amines
forms a white gas) , loading tanks and tank cars and trucks by pipeline
(i.e., no open pouring), and exhausting the loading area to the chilled
column.
• Industrial Use. The control methodology that is applicable
to industries where amines are used is basically the same as that for
the amine-manufacturing industry. The principal control techniques
are absorption by wet scrubbing, adsorption (e.g., on activated carbon),
and incineration.
Control of amine emissions from other industries may be even
more important than those from amine manufacturing. In the latter,
the product is the amine and, therefore, it is advantageous to the
manufacturer to use a closed system and to take other measures in
111
-------
order to minimize losses. In some industries (e.g., pharmaceuticals,
rubber, chemicals, tanning, pesticides), amines are used in the pro-
duction process and it is quite unlikely that they are handled in a
closed system (139). Good housekeeping practices in the plants (e.g.,
use of closed containers as much as feasible, prompt correction of
leaks, and clean-up of spills) substantially reduce the presence of
amines in the working atmosphere and, consequently, the potential for
amine emissions from the plant. Wet scrubbing or adsorption of all
gaseous effluent streams, with subsequent recovery or incineration,
will control amine emissions.
In other industries, amines are generated during the production
process (e.g., rendering). The quantities can be sizable and control
of amine emissions would serve the immediate locality because of the
concomitant odor abatement in addition to reducing (or eliminating)
the presence of amines in the atmsophere where they can be utilized
as precursors in the formation of nitrosamines. Wet scrubbing, ad-
sorption, and incineration would provide control. It should be
mentioned that incineration produces N0x gases, which have not been
effectively controlled to date.
In some industries, amines are used in wet scrubbers to control
various emissions. Carbon dioxide is scrubbed by dimethanolamine or
diethanoamine. Hydrogen sulfide is scrubbed by monoethanolamine or
diethanolamine. Ammonia, xylidine, and dimethyl aniline are used to
scrub sulfur dioxide. Although the amine solution is recovered and
112
-------
recycled through the scrubber, amines can be lost from the scrubber
to the atmsophere. The cleansed gas exiting from a scrubber is some-
times vented to a flare; this would incinerate any amines that may
have volatilized in the scrubber.
In the ASARCO process for absorption of sulfur dioxide in dimethyl
aniline solution, the exit gases from the absorber pass through a
soda scrubber and then an acid scrubber; this would remove any vola-
tilized amines from the lean gas and they could then be recovered for
recycling. It could not be ascertained whether passing gases through
another scrubber in order to recover amines lost during the amine
absorption is generally feasible and practicable. It should be noted
that there are other methods available for removal of specific com-
pounds from gas streams (e.g., activated carbon adsorbs hydrogen
sulfide) (199) ; if amine losses from scrubbers are indeed significant,
which is doubtful, these losses could be eliminated by the use of
alternate methods.
• Coking and Petroleum Refining. In the coking and petroleum
refining industries, amines are generated during the processing (200,
150) (see Figures 12 through 16). In coal gasification and lique-
faction, amines would also be produced (see Figures 17 and 18).
The processes of liquefaction and gasification are not of great
significance at this time as only a few pilot plants are utilizing
these methods. However, as the development of energy sources pro-
gresses, they may, if widely utilized, have significant impact on
the emissions of amines.
113
-------
ammonia (2,g) .
aniline (2,g) |
methylaniline (2,g)
4-aminobiphenyl (l,g)
o-naphthylamine (l,g)
P-naphthylamine (l,g)
SLOT-TYPE ~O
VOLATILE
/ COKE OVEN
PUSHING
TAR
LIQUOR
FLUSHING
LIQUOR
FUEL
GAS /aimonia (2,a,g)
aniline (2,g)
methylaniline (2,g)
4-aminopiphenyl (l,g)
o-naphthalamine (l,g)
P-naphthalamine (1,g)
COLLECTION*^
-------
DIE1HYLAKINE (2,g)
QY MFIHTLKTHYLAMIHE (2,g)
Known Present/Known Hazardous
Known Present/Suspected Hazardous
Suspected Present/known Hazardous
aqueous
gaseous
SULFUR
TO SALES
TO SALES AND
REFINERY FUEL
SWEET
'SWEET GAS
FROM PROCESSES
LPG
OLEFIN
GASES
SOUR
®—[f
SWEET
LIGHT
ENDS
'SOUR GAS
FROM PROCESSES
ENDS
~V/s///////A \
METHYLETHYLAMINE (2,g]
DIETHTLAKIHE (2,g)
"TO LIGHT
HYDROCARBON PROCESSING
SWEET
NAPHTHA
LIGHT
SOUR
littMWIA (2,g)
{77777777777]
/VACUUM '/
/DISTILLATION/^
KEROSENE
TO MIDDLE
DISTILLATE PROCESSING
DESALTED
DESALTING
CRUDE STORAGE
CRUDE
CRUDE
OIL
.UBE
TOPPED
CRUDE
VACUUM
ANURIA (2,g)|
Y//////7/A
_ 'VACUUM
Distillation; '
**sss/s/S
TO HEAVY
DISTILLATE PROCESSING
Source: Adapted fro- "Potentially Hazardous Emissions :tnm tin*^
Extraction sad Processing of Coal and Oil, EPA-650/2-
U.S. EPA, Washington, D.C. , April 1975.
STOCK
RESIDUAL
OIL
'hydrocarbon
HYDROGEN
PRODUCTION
FIGURE 13. REFINERY - CRUDE SEPARATION
PLANT HYDROGEN
-------
POLY
GASOLINE
OLEFIN
GASES
POLYMERIZATION
L.E.,
ALKLYLATION
ISOBUTANE
ALKYLATE
ISOBUTANE
\S\LIGHT\\^
HYDROCARBON
\STORAGE
\ BLENDING \
N-BUTANE
AMMONIA (2,a)
ALIPHATIC AMINES (2,a)
\ROMATIC AMINES (2,a)
ISOMERATE
ISOMERIZATION
SWEET
NAPHTHA
L.E.
IOMATIC!
-------
LIGHT
ENDS
FLUID BED
j/CAT. CRACKER
GASOLINE
AMMONIA (2,a)
AROMATIC AMINES (2,a)
NITROSAMINES (3,g)
CHEMICAL
SWEETENING
DESULF.
"INTERMEDIAT
HYDROCARBON
STORAGE & BLENDING
LIGHT
ENDS
MOVING BED
/ CAT CRACKER/^
///////
CAT.
GASOLINE
LIGHT
ENDS
AMMONIA <2,a)
ALIPHATIC AMINES (2,a)
AROMATIC AMINES (2,a)
FUEL
AMMONIA (2,a)
' KEROSENE HDS^
AROMATIC AMINES (2,a)
NITROSAMINES (3,g)
DESULF
KEROSENE
AMMONIA (2,a)
LIGHT
ENDS
„ CATALYTIC
HYDROCRACKING
GAS OIL
AMMONIA (2,a)*—
CAT.
GASOLINE
LIGHT
ENDS
GAS OIL
^GAS OIL HDSX
DESULF
VACUUM OIL
AMMONIA (2,a)
DEASPHALTED
1 - Known Present/Known Hazardous
2 - Known Present/Suspected Hazardous
3 - Suspected Present/Known Hazardous
a - aqueous
g - gaseous
Source: Adapted from "Potentially Hazardous Emissions from the
Extraction and Processing of Coal and Oil," EPA-650/2-75-038,
U.S. EPA, Washington, D.C., April 1975.
FIGURE 15
REFINERY-PROCESSING OF INTERMEDIATE HYDROCARBONS
-------
STEAM BOILER
AtMOMIA (2,a)
AmONIAf (2,a)
V/////////A
RESIDOAL OIL HDS
Known Present/Known Hazardous
Known Present/Suspected Hazardous
Suspected Present/Known Hazardous
AIMMU (2,a) ~
MITROSAKIKES (3,g) •—
AXOMATIC AMINES <2,g)
Source: Adapted froa "Potentially Hazardous Emissions from the
Extraction and Processing of Coal and Oil," EPA-6S0/2-75-O38,
U.S. EPA, Washington, D.C., April 1975.
FIGURE 16. REFINERY - PROCESSING OF HEAVY HYDROCARBONS
-------
Known Present/Known Hazardous
Known Present/Suspected Hazardous
Suspected Present/Known Hazardous
(RECTISOL WASH)
FURTHER GAS
TO PIPELINE
(RECTISOL. WASH)
LIQUOR
AI»OHIA (2,g) v. X
DIETHTLAMIXES (2,g)
METHYLETHYLAMIHES (2,g)
LIQUOR
'SULFUR RECOVERY ^
'/(STRATFORD PROCESS)/'
\//s///}////ssss
LIQUOR
AMKW1A (2,a)
Mt£U£M6""\
''(PHAHOSOLVAM PROCESS)'
'///////////S/Ss
LIQUID
/////;?, .
///QUIWCHIRG
•V/AM) COOLIBC'//
/////////////;
A»©HIA (2,a,g)
TAR, OIL'
Source: Adapted fro* Potentially Hazardous Emissions fraa the
Extraction and Processing of Coal and Oil," EPA-650/2-73-038,
U.S. EPA, Washington, D.C., April 1975. FIGURE 17. COAL GASIFICATION PROCESS MODULE
-------
TO PLANT FUEL
GAS
CO
SULFUR
RECOVERY
GAS
TO SALES
OFF
WATER TREATMEKTl
WATER
"•SEPARATOR^
PREPARED
OIL,
GAS
NAPTHAS
HYDROTREATINC
NAPTHAS
REACTION
PRODUCTS
COAL
SLURRY
SLURRY
PREP
FILTRATION
REACTOR
STORAGE
SLURRY
SEPARATOR
KETHYLETHYLAM1NE (2,a)
DIETHYLAMIDE (2,a) 1 /
AMMONIA (2, a)
OILS
SOLVENT
KEY
1 - Known Present/Known Hazardous
2 - Known Present/Suspected Hazardous
3 - Suspected Present/Known Hazardous
a - aqueous
FILTER
CAKE
TO CASIFIER
Source: Adapted froa "Potentially Hazardous Eaissions froa the
Extraction and Processing of Coal and Oil," EPA-650/2-75—038
U.S. EPA, Washington, D.C., April 1975.
flGUftE 18. COAL LIQUEFACTION PROCESS MODULE
-------
The hatching in Figures 12 through 18 indicates possible sites
of amine emissions. At each of these steps are listed the specific
amines which could enter the environment if emissions actually occur.
These emissions were determined after a process of evaluating each
chemical for its importance, physical state and concentration, and
reactivity in using material balances and engineering estimates (150).
Amine absorbers are used for recovery of hydrogen sulfide, which
usually is transferred to a sulfur recovery unit or to a sulfuric
acid plant. Amine absorbers are used in the recovery section of the
fluid catalytic cracking unit and, therefore, in such processes as
catalytic cracking of virgin and cycled oils; catalytic reforming
and desulfurization of naptha, kerosene, jet and diesel fuels, and
residual fuel oil; and coking. The amine absorber unit contains mono-
ethanolamine (15-20% solution) or diethanolamine (20-30% solution) and
does present odor problems, which indicates the loss of amines (201).
In addition, dimethanolamine and diethanolamine are used for
scrubbing carbon dioxide. Ammonia, xylidine, and dimethyl aniline
are used for scrubbing sulfur dioxide. There is potential loss of
amines from these scrubbers as well.
Emissions from oil refineries can be controlled by three types
of procedures—change in processing, installation of control equipment,
and improved housekeeping (202) . All three would curtail emissions
that arise during processing. Only the first two could have some
impact on the losses from amine absorbers. It is unlikely that changes
121
-------
in processing procedures could or would be instituted; they would
probably be feasible to a great extent only in new refineries—that is
in those not yet in operation. The best procedure for control of
amine emissions is the installation of control equipment. Wet scrubbers
constitute an effective vapor recovery system; the lean gas should be
vented to incinerators. Vapor phase adsorption systems are also ef-
fective. Improved housekeeping procedures would entail better main-
tenance as well as employee education; however, the impact on total
emissions would be rather small.
• Incineration and Combustion. Another potential source of amine
emissions to the atmosphere is the incineration of organic materials.
Incineration includes: (1) industrial combustion; (2) incineration of
wastes; and (3) accidental fires.
It is unlikely that combustion in power plants would be a direct
source of amines , since the combustion would be as efficient as possible
in order to ensure maximum power production (137) . However, hydrazine
and amines are used for oxygen control in the boiler feedwater in
steam electric power plants (201), and amines could be inadvertently
lost from this control system.
The incineration of solid wastes is a likely source of amine
emissions because municipal and commercial incinerators do handle
organic wastes. The efficiency of the operation and the controls used
vary greatly. In municipal incinerators, the maintained temperatures
are usually insufficient and applied control technology is inadequate.
122
-------
However, although incinerators can be a source of amines, they can also
be a means of control if proper conditions are maintained. Proper
incineration conditions would preclude the release of amines to the
atmosphere. Wet scrubbers (preferably acidic) on the stacks could
absorb any volatile amines , which could then be passed through the in-
cinerator again. Increased energy requirements and higher costs are
factors in the application of this control technology.
Accidental fires in forests, solid waste dumps, and homes probably
involve incomplete combustion and, therefore, the release of amines;
no controls are feasible for this source. Accidental fires constitute
a relatively small source of amines to the atmosphere.
• Sewage Treatment. Sewage treatment plants constitute localized
sources of amines that are products of the decomposition of organic
matter (137 ,152) . At present, there are about 15 ,000 sewage treatment
plants in operation in the United States, including public as well as
private (industrial and commercial) facilities (203) . "Primary"
treatment usually involves settling ponds and filtration. At the
plants which provide at least some degree of "secondary" treatment,
the sewage is treated biologically; the nitrogenous compounds present
after this level of treatment are ammonia, amines, and nitrates (204).
Of the plants that provide Advanced Wastewater Treatment (AWT) (i.e.,
advanced biological or chemical treatment), fewer than 200 use the
nitrification and denitrification processes which convert the nitrogen
in nitrogenous compounds to molecular nitrogen (Nj) (203). The cost
123
-------
of AWT technologies is high compared with the cost of "secondary"
treatment (205) .
• Rendering Plants. Rendering plants constitute a source of
atmospheric amines, and the odors emanating from these plants are
evidence that amines are being emitted. Although stringent sanitation
measures can substantially reduce amine formation in other parts of
the plants, the rendering processes generate amines. Hoods and ventil-
ating systems are used to remove amines from the in-plant air. Various
methods can then effect control of amine emissions; these involve
adsorption, absorption, or incineration. Packed towers containing
activated carbon are effective in removing low concentrations of
amines from large volumes of air, provided the temperature is below
120°F and the moisture content is less than 11.5 percent. Wet
scrubbing (e.g., using 0.2 percent calcium hypochlorite) is an
effective absorption technique. Incineration is the principal method
used to control rendering plant odors. However, costs are high when
amine concentrations are low in a large volume of exhaust gas and/or
when the moisture content is high. Consequently, condensers frequently
precede the incinerators and the condensate is sewered; this would
control amine emissions to the atmosphere although they would be
discharged with the aqueous effluent (206).
« Natural Sources. Amines are formed in the decomposition of
proteins; hence, amines are the product of the decomposition of all
organic matter. The natural decomposition process—e.g., those
124
-------
occurring in peat bogs and marshes—cannot be controlled by man
except by the destruction of such ecosystems. This, of course, is
not feasible. Consequently, these areas will always constitute a
local source of amines.
Organic decomposition is a general source of amines throughout
the world. There is the decay of dead animal and plant matter, and
the decay of animal wastes , as well as the decay of the organic matter
that man has refined and used and spread throughout his environment.
Man has no control over dead plant and animal matter decomposing in
the natural environment.
• Pesticides. Pesticides have been used for many years through-
out the environment—that is, in natural areas as well as on cultivated
land and in urban areas. Many are amlne-based compounds and their
wide use in the past makes them a source of amines in the atmosphere.
They can reach the atmosphere directly by evaporation or indirectly
by decomposition. Control, other than prohibition of use, is not
possible.
In the future, this source of amines could be controlled somewhat
by using pesticides more discriminantly. In addition, dusting and
spraying should be limited to essential situations in which alterna-
tive methods of application would be Ineffective or otherwise unsuit-
able.
• Drugs. Drugs constitute an additional source of amines that,
in most instances, are used deliberately. Application can be topical
125
-------
(i.e., ointments, creams, salves, and sprays) or internal. Control,
other than prohibition of use, is not feasible.
NO Gases
x
NO gases may be precursors in the secondary formation of nitro-
X
samines (see Section II .E.2., Environmental Occurrence and Formation).
NO^ gases are generated during the combustion of organic material.
Potential sources of NO^ are process heaters, boilers, compressor
engines, catalyst regenerators, and flares. N0x gases are emitted
by petroleum refineries, fossil fuel power plants, refuse incinerators,
coffee roasters, and automobiles, as well as by diverse plants where
any of the particular NOx~generating devices may be used (150,157,200,
201,205,207,208) .
The complete removal of NO from gaseous effluents is not yet
technically feasible on a commercial basis (201). Various catalysts
are currently in the process of being developed and tested (208).
Catalytic reduction and sorption can be effective for small volumes
of exhaust gases, while catalytic conversion would be necessary for
large-scale combustion units (208) .
An alternate approach to control of N0x emissions to the atmos-
phere is reduction in N0x formation. This can be achieved, for
example, in large-scale burners, such as those associated with fossil
fuel power plants (20). The combustion source can be redesigned
to give a two-stage combustion process with tangetial, instead of
horizontal, firing. The chemistry of the combustion process can be
126
-------
changed by changing the fuel and/or by introducing fuel additives.
Although it is known that NO^ emissions vary with the type of fuel
(they are greatest with coal, less with fuel oil, least with natural
gas), the current energy crisis precludes exercising the option of
choice of fuel at this time. Also, reducing NO emissions from power
plants by reducing temperatures might increase nitrosamine emissions.
Other possible modifications of combustion techniques include improved
burner design, reduced load, low excess air firing, and flue gas
recirculation (201) .
• Nitrates/Nitrites. Nitrates and nitrites have been introduced
to the environment throughout the world in the form of fertilizers.
There is little likelihood that these compounds volatilize. The
method by which the fertilizers are applied to the soil can disperse
them in the atmosphere. The usual method of application, via a
fertilizer spreader, can result in the fertilizers' being suspended
in the air—either as fine particles or attached to particulates.
If the fertilizer is soluble, it is sometimes dissolved in the
irrigation water and applied by sprinkling; this method would increase
the probability that the fertilizers could volatilize. Controls might
be feasible, but the impact would be small.
Nitrates and nitrites occur naturally throughout the world in
soils as well as in water and living and decomposing organic matter.
They can be removed from sewage by denitrification, and AWT technology.
Otherwise, it is not feasible to control the presence of nitrates
127
-------
and nitrites in the environment, excepting those found in foodstuffs.
Nitrates and nitrites are added to meats during the curing and handling
processes and these could contribute to in vivo nitrosamine formation.
At this time, however, the FDA is planning to limit the permissible
levels of these compounds in foods.
128
-------
III. CONCLUSIONS AND RECOMMENDATIONS
The following specific conclusions can be drawn concerning the
chemical activity and reactivity of nitrosamines .
CHEMICAL ACTIVITY
• Based on the chemistry of nitrosamine formation and the kinetics
of amine nitrosation, only secondary amines and a few tertiary amines
(of high volatility) readily react with nitrous acid to form nitrosamines.
Therefore, only emissions of these amines will be of consequence during
secondary formation.
• Gaseous nitrosamines are characteristically photosensitive
and can be denitrosated to their precursors by both visible and ultra-
violet light. Therefore, secondary synthesis may be a cyclic process.
However, because of their photolability, nitrosamine buildup in the
atmosphere is not likely.
• There exist metallic catalysts that may facilitate nitrosamine
formation under conditions that would ordinarily not have induced
nitrosation. As a result, nitrosamine formation may occur in atmos-
pheres containing lower contaminant concentrations than expected.
However, this action is not completely documented, and is speculative
at this time.
• The kinetics of amine nitrosation in solution follow a dinitro-
gen trioxide mechanism and these reactions may have a bearing on the
atmospheric burden as the compounds may volatilize from the water or
soil into the ambient air. Alsothese reactions may occur in water
droplets or particulate matter in ambient atmospheres.
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• The versatility and potency of nitrosamines administered to
animals indicates that, although only liver damage has been documented
in humans , carcinogenic hazards may be incurred by humans exposed to
nitrosamines. This may be applicable only to in_ vivo nitrosamines,
rather than atmospheric exposure.
• Artifact formation in cold traps initially thought to be a
significant problem increasing the nitrosamine content of an air sample
only accounts for a very small quantity of nitrosamine formation. As
a result, the nitrosamine concentrations detected and reported are
probably accurate.
• Individuals residing or working in areas of amine emissions,
and high NO^ concentrations may be risking exposure to nitrosamines
as it has been established that under certain conditions amines may
nitrosate in polluted urban atmospheres. Individuals exposed to
direct emissions of nitrosamines may be incurring a higher degree of
risk.
As a result of these conclusions and the detection of atmos-
pheric nitrosamines, the need has arisen for determination of the
hazard presented by these compounds to the human population, and of the
source(s) of the compounds, and for synthesis of a plan of action to
deal with the hazard.
DETERMINATION OF THE HAZARD
The potential risk to humans must be extrapolated from the data
compiled pertaining to the experimental laboratory exposure of animals.
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Although this is not a definitive or completely accurate method, the
probability of danger can be deduced. Nitrosamines have been found
to be versatile carcinogens in many animal species, including non-
human primates, with different compounds inducing tumors in various
locations. In these experiments, the usual mode of application is
oral, either with the food or via gastric intubation with small daily
aliquots appearing as quite efficient doses. Due to the dangers
inherent in the use of these compounds, only isolated reports of in-
halation studies conducted on experimental animals were found in the
literature. In these studies, tumors of the nasal cavity, trachea,
lung, throat, liver, and kidney were reported, suggesting that inhala-
tion may be as effective as oral dosage. Therefore, it appears that
a risk to the human population may exist due to atmospheric nitro-
samines .
SOURCES OF THE COMPOUNDS
From the evaluations of the formation of nitrosamines, it is
apparent that there are several possible pathways of entry into the
environment. The first mode, which is the most readily controllable,
is via actual synthesis of the compound as a desired product. There
are five companies currently engaged in production of N-nitrosodiphenyl-
amine, which does not present a carcinogenic threat according to the
existing scientific experimentation. Two additional companies manu-
facture small quantities of various nitrosamines, experimentally
utilized by the scientific community. Due to the awareness of hazard,
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the synthesis of these compounds is performed in containment facilities.
These sources, therefore, should account for little, if any, environ-
mental contamination.
The use of dimethylnitrosamine during the production of hydrazine
by the FMC Corporation constitutes the second source. Although syn-
thesis occurs in a closed system, the disposal of waste material and
the danger of accidental leakage during production and utilization of
the nitrosamine poses a significant threat. The use of the hydrazine
as a hypergolic rocket fuel by the U.S. Air Force may also be a
source of environmental nitrosamine. The possibility is substanti-
ated by the detection of residual nitrosamines, partial oxidation
products of the hydrazine fuels used, on the Surveyor III camera.
An additional pathway exists as a source of environmental nitro-
samines , de novo or secondary formation. As a result of the detection
of nitrosamines in vivo after administration of an amine and a nitro-
sating agent, it was speculated that this method of formation from
precursors could occur atmospherically, and this hypothesis was recently
confirmed. Formation and degradation rates for DMN were elucidated
utilizing dimethylamine and NC>x, nitrous acid, and water vapor in
expected environmental concentrations. In polluted atmospheres
containing high concentrations of sufficient N0x, nitrous acid, and
amines, measurable quantities of DMN were synthesized. The photolytic
degradation rate for this compound was calculated to be between 30
minutes and one hour. Therefore, it is likely that, under the proper
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conditions, nitrosamines could accumulate during the dark photoperiod
with subsequent degradation, perhaps to the precursors, during sunlight.
This source of nitrosamines may be significant in determining the
environmental burden of nitrosamines.
Precursor amines may be found in emissions from amine production
facilities as well as from industries that utilize amines during the
synthesis of other compounds and products. In addition to these
sources, amines are released to the environment during the decomposi-
tion of plant, animal, and waste matter. Precursor N0x is released
to the environment primarily during combustion of fossil fuels in
the form of coal and oil. Two naturally occurring processes, bacter-
ial degradation and slow reactions of fossil fuels, also contribute
to the environmental burden of N0x. Due to the widespread availability
of the precursors, both from natural and anthropogenic sources, this
is also the method that will require the most complex control strategy
if it is deemed necessary. An additional pathway involves the degrada-
tion of more complex compounds to nitrosamines under environmental
conditions and, as this mode involves only a few substances, control
would not be complex.
SYNTHESIS OF AN ACTION PLAN
The control technology applicable to the FMC plant involves
scrubbers in the stacks, as this appears to be the source of the at-
mospheric DMN from the facility. Complete combustion of the waste
material would destroy the nitrosamine, alleviating the contamination
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problem. Control technology for secondary formation involves amine
and/or NO^ emission reduction methodologies. (This action would
apply only if this pathway were confirmed to be a major contributor to
the environmental burden.) These techniques would have to be imple-
mented in the major locations determined as emitters of the precur-
sors , which may constitute a sizable portion of the industrial
community.
Further information is essential for the formulation of a realis-
tic and oomplete control strategy for the reduction of atmospheric
nitrosamines. Several areas of investigation, if pursued, will
enlarge the knowledge base as well as denote the appropriate approach
for resolution of the problem.
TECHNICAL RECOMMENDATIONS
1. Evaluation of the nitrosamine sampling and identification
techniques presently available. A collection and analysis system
that affords mobility and on-site determination as well as precision
and reliability will be the most desirable. The GC/TEA system, set
up as a vehicular unit, will allow the necessary portability. Con-
current sampling using a cold trap or Tenex and subsequent freezing
of the sample with transport to a facility with gas chromatography/
mass spectrometry capability may suffice as confirmation of sampling
data until such time as one method with both portability and accepted
accuracy can be devised.
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2 . Initiation of Inhalation studies to document the health
effects associated with the low levels of nitrosamines found In
ambient air. Although extrapolation of experimental animal data into
significance to the human population is not definitive, it is the
only viable alternative in determining the risk presented by atmos-
pheric nitrosamines . By using concentrations of the compounds that
correspond to the exposures expected for the human population, the
definition of risk would be facilitated.
The experimental design problems incurred during instigation of
these investigations will be many and varied. The primary difficulty
will be establishing the number of animals utilized. The sensitivity
of animal test systems is such that often they only detect carcino-
gens which occur at a relatively high frequency. For example, if a
compound induced cancer in one out of 10,000 people exposed, several
times 10,000 animals would be required to obtain statistically signif-
icant data. This number would have to be increased further if the
animals were suspected of being less susceptible to the compound than
humans. Even utilizing high doses to compensate for the problem,
only carcinogens with relatively high incidences of cancer induction
can be detected, as administration of these high doses often kills
the animal immediately from other causes. In the case of atmospheric
nitrosamine exposure, further difficulties will arise in terms of the
availability of suitable containment facilities as well as in terms
of the possible dangers of maintaining the experimental animals
(i.e., feeding, watering, cleaning cages, and examining).
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The inception of human epidemiological studies is also indicated;
however, actual methods and levels of exposure will be difficult to
document for those individuals who have been exposed to industrially
produced or utilized nitrosamines. However meager the data appears
initially, it may reveal a higher incidence of a debilitating illness
in those individuals who have been exposed, which could confirm the
danger of ambient nitrosamines.
3. Determination of the principle source of atmospheric
nitrosamines. Documentation and quantificaiton of the formation
of these compounds from precursors must be performed. The effects of
temperature, light, pH, possible catalysts or inhibitors, and concen-
tration of reactants should be examined in conjunction with these
studies. Additional investigations of the chemical stability and
reactivity of these compounds, under conditions that simulate the
heavily polluted environments in which they are expected to be found,
may reveal properties that can be utilized in formulation of compre-
hensive control strategies . Determination of these parameters would
facilitate measurement of reaction degradation rates pertinent to the
environmental problem. It would also dictate the areas in which
controls could be applied with success. This investigation will be
simplified by adoption of the following recommendation.
4. Expansion of the monitoring network to include suspected
areas of nitrosamine occurrence. The most important sites for evalua-
tion are : coking plants , refineries , incinerators , food processing
136
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locations, areas of high nitrogen oxide emissions, power plants,
synthetic fuel production facilities, and any sources suspected of
having direct nitrosamine emissions. Amine production facilities that
are located in cities which have high NC^ concentrations would also
be logical candidates for inclusion in monitoring studies if it were
determined that they could contribute to the nitrosamine pool. Addi-
tional useful information that could be simultaneously compiled in-
cludes quantification of the distribution and availability of precursors,
including nitric oxides and amines. Expansion of detection techniques
and methodologies would be necessary for evaluation of atmospheric
amines ; however, the data would be valuable in establishment of loca-
tions for further monitoring.
5. Investigation of the roles of codistillation and evapor-
ation of nltrosamines from aqueous surfaces. This activity could have
impact on the ambient atmospheric nitrosamine pool. If these atmos-
pheric nitrosamines were absorbed on ambient particulates, this could
significantly alter both the reactivity of the compound and its
controllability. Simultaneous particulate contaminants may also
significantly affect the particulate behavior of absorbed nitrosamines.
6. Development of control technology for amine emissions.
A cost-feasibility analysis of the methodology available for regula-
tion of amine emissions to the atmosphere should be initiated. As
amines are diverse in nature and are utilized in a variety of product
synthesis operations, technology may need to be reformulated, taking
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into account the cost of installation and maintenance of the equipment.
Some of the established technology may be valuable and useful or it
may need to be integrated with new technologies (e.g., ultraviolet
light degradation of nitrosamines).
7. Investigation of substitutes for nitrates/nitrites.
Although the principal purpose of this document was to evaluate atmos-
pheric nitrosamines , the research conducted during preparation of this
report brought to light the problem of the nitrate/nitrite content of
foodstuffs. The addition of these compounds to meat products has an
effect on the color and taste of the meat as well as having a preserv-
ative effect. Although the removal or reduction of these substances
from meat is advisable due to the possibility of in vivo nitrosamine
formation, it may have an unfavorable impact on the palatability and/or
the longevity of freshness of these products. Substitutes for nitrates/
nitrites may be developed; however, thorough testing for deleterious
health effects as well as for satisfactory replacement properties
should be instigated before substitution.
If it is determined to be necessary, implementation of these
recommendations will facilitate the formulation of a complete strategy
for the reduction of atmospheric nitrosamines to non-hazardous levels
as well as developing the technologies necessary for control. Until
all the data have been compiled, it would be most judicious to assume
that nitrosamines in the atmosphere do present a possible hazard to
the exposed human population, and that known sources of these compounds
should be controlled.
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155
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APPENDIX A
AMINES MANUFACTURING AND DISPERSIVE USE
At-1
-------
MFG OF
METHYLAMINE
losses
SCRAP
STORAGE
W,A
A,T
DISPOSAL
1.65x10 tons
V 1972 ^
losses
MFG OF
DYES
W,A
MFG OF
INSECTICIDES
AND
FUNGICIDES
losses
loss in
use
W, A
DYE FOR
ACETATE
TEXTILES
losses
MFG OF
SURFACTANTS
application
TANNING
AGENT
ro
losses in
use
A,W
FUEL
ADDITIVE
.A.T
losses
loss in
f PAINT \
f REMOVER '
[(POLYMERIZATION,
V INHIBITOR)J
MFG OF
PAINT
REMOVER
loss in
use
PHOTOGRAPHIC
DEVELOPER
losses
MFG OF
PHARMACEUTICALS
MFG OF
RUBBER
(ACCELERATOR)
losses
FIGURE 1. POSSIBLE ROUTES OF METHYLAMINE INTO THE ENVIRONMENT (1°)
-------
/ MFG OF >
DIMETHYL AMINE
losses
SCRAP
STORAGE
A,T
DISPOSAL
UtA
4.75x10 tons
s. 1972 /
"SCRUBBER F0E\ losses
ACID GAS 1
A,W
losses
MFG OF
DYES
V,A
MFG OF
FLOTATION
AGENT
losses
vaporization
losses
GASOLINE
STABILIZER
leaching
W,T
DUMPS
MFG OF
TEXTILES
TEXTILES
MFG
RUBBER
(ACCELERATOR)
losses
losses
(vaporization)
losses
INCINERATOR
losses
MFG OF
PHARMACEUTICALS
A,V
losses in
V,A
PESTICIDE
MANUFACTURE
(PROPELLANT)
application
losses
losses
MFG OF
SURFACTANTS
A,W
W, A
FIGURE 2. POSSIBLE ROUTES OF DIMETHYLAMINE INTO THE ENVIRONMENT (2°)
-------
MFG OF
TRIHETHYLAMINE
losses
SCRAP
STORAGE
A,T
W,A
DISPOSAL
1.4x10 tons
1972
WARNING
AGENT
FOR
NATURAL
" GAS '
leaks
use
^ MFG OF \
DISINFECTANTS
losses
A,W
MFG OF
FLOTATION
. AGENT
uses
INSECT
ATTRACTANT
use
a.w.t
losses
A,W
losses
MFG OF
PLASTICS
A,W
FIGURE 3. POSSIBLE ROUTE OF TRIMETHYLAMINE INTO THE ENVIRONMENT (3°)
-------
MFG OF
ETHYLAMINE
4
1.7x10 tons
1972
losses
SCRAP
STORAGE
•i?,A
DISPOSAL
losses
MFG OF
DYES
¥,A
losses
PETROLEUM
REFINING
W,£
J»
Ol
MFG OF
RUBBER
STABILIZER FOR
, RUBBER LATEX ,
losses
losses
MFG OF
DETERGENTS
use
DETERGENTS
,W,A,
,W,A.
losses
FIGURE 4. POSSIBLE ROUTES OF ETHYLAMINE INTO THE ENVIRONMENT (1°)
-------
MFG OF
DIETHYLAMINE
losses
SCRAP
STORAGE
A,T
DISPOSAL
sS?,A
4.75x10 tons
1972
./MFG OF \
RUBBER
(ACCELERATOR)
losses
vaporization
N. leaching
DUMPS
W,T
MFG OF
TEXTILES
(FINISHING
AGENT)
TEXTILES
losses
(vaporization
losses
INCINERATOR
losses
MFG OF
DYES
losses
' MFG OF
FLOTATION
. AGENT
use
losses
MFG OF
PESTICIDES
losses
MFG OF
RESINS
losses
PETROLEUM
REFINING
,W,A
losses
MFG OF
PHARMACEUTICALS
FIGURE 5. POSSIBLE ROUTES OF DIETHYLAMINE INTO THE ENVIRONMENT (2°)
-------
losses
MFG OF
TRIETHYLAMINE
SCRAP STORAGE
DISPOSAL
A,W
losses
MFG OF
RUBBER
(ACCELERATORS)
application
A,W
A,W
losses
application
A.W,
PROPELLANT
A,W,T
f CURING AND >
HARDENING AGENT
V for polymers y
use
W,A
MFG OF
WETTING,
PENETRATING &
WATERPROOFING
\ AGENTS ^
FIGURE 6. POSSIBLE ROUTES OF TRIETHYLAMINE INTO THE ENVIRONMENT (3°)
-------
losses
SCRAP
STORAGE
MFG OF
METHYLDIETHYLAMINE
A,W
DISPOSAL
DESALINATION OF
BRACKISH WATER
V /
use
FIGURE 7. POSSIBLE ROUTES OF METHYLDIETHYLAMINE INTO THE ENVIRONMENT (3°)
-------
MFG OF
n-BUTYLAMINE
losses
SCRAP
STORAGE
A,W
DISPOSAL
A,T
0.5x10 tons
1972
MFG OF
EMULSIFYING
AGENTS
losses
A,W
MFG OF N
PHARMACEUTICALS
losses
A, W
losses
MFG OF
INSECTICIDES
A, W
MFG OF
RUBBER
ACCELERATORS
losses
A,W.
losses
MFG OF
DYES
A,W
MFG OF
TANNING
AGENTS
losses
A.W,
FIGURE 8. POSSIBLE ROUTES OF n-BUTYLAMINE INTO THE ENVIRONMENT (1°)
-------
losses
MFG OF
t-BUTYLAMINE
SCRAP
STORAGE
A,T
DISPOSAL
A,W
MFG OF
RUBBER
(ACCELERATORS)
losses
A,W
MFG OF
INSECTICIDES
AND
FUNGICIDES„
application
loss
A ,W
losses
MFG OF
DYES
A,W
losses
MFG OF
PHARMACEUTICALS
A,W
FIGURE 9. POSSIBLE ROUTES OF t-BUTYLAMINE INTO THE ENVIRONMENT (1°)
-------
losses
SCRAP
STORAGE
A,W
DISPOSAL
losses
A,W
^ MFG OF ^—
RUBBER ^
ACCELERATORS)
losses
A,W
losses
A,W
losses
MFG OF
DYES
A,W
losses
A,W
application
MFG OF
FLOTATION
^ AGENTS
^ MFG OF \
INSECTICIDES
MFG OF ^
EMULSIFYING
AGENTS .
MFG OF
DI-n-BUTYLAMINE
^ 7
A,W,T
V
FIGURE 10. POSSIBLE ROUTES OF DI-n-BUTYLAMINE (2°)
-------
SCRAP
STORAGE
/ MFG OF \
1,2 DIMINOPROPANE
losses
DISPOSAL
A,W|
/ MFG OF \
PHARMACEUTICALS
losses
A, W
losses
MFG OF
DYES
A,W
X^MFG OF
RUBBER
(ACCELERATORS)'
losses
A,W
FIGURE 11. POSSIBLE ROUTES OF 1,2 DIAMINOPROPANE INTO THE ENVIRONMENT (1°)
-------
>
I
losses
SCRAP
STORAGE
MFC, OF
ALLYLAMINE
A,W
A, T
DISPOSAL
losses
MFG OF
DYES
A,W
losses
A,W
losses
MFG OF
INSECTICIDES,
A,W
A,W
losses
application
MFG OF
DETERGENTS
a.w.t
use
use
losses
A,W
GASOLINE
ADDITIVE
losses
A,W
MFG OF
RUBBER
CHEMICALS
MFG OF
FLOTATION
_ AGENTS .
^ MFG OF \
'HARMACEUTICALS,
use
A,T
FIGURE 12. POSSIBLE ROUTES OF ALLYLAMINE INTO THE ENVIRONMENT (1°)
-------
SCRAP
STORAGE
DISPOSAL
EMULSIFIER
losses
losses
MFG OF
POLISHES
application
MFG OF
COSMETICS
MFG OF
SOAPS
AND
DETERGENTS
application
MFG OF
AGRICULTURAL
SPRAYS
application
losses
losses
A,W
SCRUBBER FO]
ACID GAS
losses
application
MFG OF
PAINTS
MFG OF ^
ETHANOLAMINE
11x10 tons
\ 1972 .
.A,W,
FIGURE 13. POSSIBLE ROUTES OF ETHANOLAMINE INTO THE ENVIRONMENT (1°)
-------
Ul
losses
SCRAP
STORAGE
W,A
DISPOSAL
A, T
A,W
LIQUID
DETERGENT
losses
losses
A,W
MFG
EMULSION
PAINTS
application
A,W
losses
A,W
losses
MFG OF
2 ,4.D
(SOLUBILIZER)
application
T, A,W
application
MFG OF
CUTTING
OIL
MFG OF
RESINS &
PLASTICIZERS
losses
A,W
A,W
losses
application
MFG OF
SHAMPOOS
A ,W
losses
MFG
CLEANERS
application
POLISHES
/ MFG OF \
DIETHANOLAMINE
FIGURE 14. POSSIBLE ROUTES OF DIETHANOLAMINE INTO THE ENVIRONMENT (2°)
-------
losses
MFG OF ^
JRIETHANOLAMIN]
SCRAP
STORAGE
A,W
DISPOSAL
COSMETICS
WOOL
SCOURING
AGENTS
open burning
vaporization
\ leaching
FATTY
ACID
SOAPS
DUMP
SHAMPOOS
MFG OF
TEXTILES .
ANTIFUME
AGENT
WATER
REPELLANT
TEXTILES
use
DRYCLEANING
INCINERATOR
/MFG OF \
PLASTICS
PLASTICIZER'
losses
A,W
FIGURE 15. POSSIBLE ROUTES OF TRIETHANOLAMINE INTO THE ENVIRONMENT (3°)
-------
losses
MFG OF
METHYLETHANOLAMINE
SCRAP
STORAGE
open burning
vaporization
DISPOSAL
leaching
DUMPS
MFG OF
TEXTILES
TEXTILES
losses
losses
MFG OF
PHARMACEUTICALS
INDINERATOR
FIGURE 16.
POSSIBLE ROUTES OF METHYLETHANOLAMINE INTO THE ENVIRONMENT (2°)
-------
/ MFG OF \
ETHYLENEDIAMINE
losses
SCRAP
STORAGE
W,A
A> J.
DISPOSAL
3.1x10 tons
\ 1972 .
OPEN
BURNING
losses
.losses
MFG OF
RUBBER
(ACCELERATOR)
STABILIZER
FOR
RUBBER LATEX
A,W
MFG OF
ANTIFREEZE
(CORROSION
INHIBITOR)
application
A,f
A.W
leaching
DUMPS
losses
00
MFG OF
TEXTILES
(LUBRICANT)
losses
MFG OF
DYES
TEXTILES
INCINERATOR
MFG OF
HEAT
SENSITIVE
ADHESIVES
application
application
HIDE
DEHAIRER
A.W,
FIGURE 17. POSSIBLE ROUTES OF ETHYLENEDIAMINE INTO THE ENVIRONMENT (1°)
-------
losses
SCRAP
STORAGE
A,T
A,W
DISPOSAL
losses
MFG OF
NYLON
A,W
MFG OF
HEXAMETHYLENEDIAMINE
^— 3.07x10"* tons/^
1973
FIGURE 18. POSSIBLE ROUTES OF HEXAMETHYLENEDIAMINE INTO THE ENVIRONMENT (1°)
-------
ro
O
losses
SCRAP
STORAGE
T, A
DISPOSAL
losses
MFG
RUBBER
(ACCELERATOR)
losses
£,W
application
a.w.t
\l
ELASTICIZING
CELLULOSE
FIBRES
losses
losses
A.W,
losses
MFG
WATER PROOF
GLUE
MFG
EXPLOSIVES
A,W
losses
MFG \
DISINFECTANT
FUMIGANT
CITRUS
.FUNGICIDE /
PLASTICS
(CURING
s>AGENTix
MFG
RESINS
MFG
HEXAMETHYLENE
TETRAMINE
3.35x10 tons
\. 1973
FIGURE 19. POSSIBLE ROUTES OF HEXAMETHYLENETETRAMINE INTO THE ENVIRONMENT (1°)
-------
^ MFG OF ^
ETHYLENEIMINE
losses
SCRAP
STORAGE
DISPOSAL
0.25x10 tons
\ 1972 /
r FLOCCULANT
FOR
fATER TREATMEN'
ANCHORING ^
AGENT FOR FILM
< LAMINATION >
PRIMING
AGENT
FOR
PRINTING
MFG OF
SURFACE
ACTIVE
AGENTS
losses
OPEN BURNING
VAPORIZATION
losses
MFG OF
PESTICIDES
DUMPS
FUEL OIL &
LUBRICANT
REFINING
losses
"PROTECTIVE^
COATING FOR
TEXTILES
AND
N. PAPER /
TEXTILES
& PAPER
MFG OF
ADHESIVES
losses
INCINERATOR
losses
MFG OF
PHARMACEUTICALS
MFG OF
ION
EXCHANGE
RESINS
losses
FIGURE 20. POSSIBLE ROUTES OF ETHYLENEIMINE INTO THE ENVIRONMENT (2°)
-------
ro
r\s
losses
MFG OF
BENZYLAMINE
SCRAP
STORAGE
A,W
DISPOSAL
losses
MFG OF
DYES
A,W
losses
A, W
losses
MFG OF
POLYMERS
A,W
MFG OF
PHARMACEUTICALS
FIGURE 21. POSSIBLE ROUTES OF BENZYLAMINE INTO THE ENVIRONMENT (1°a)
-------
MFG OF
ANILINE
losses
SCRAP
STORAGE
A,W
DISPOSAL
A.T
2x10 tons
1973
losses
MFG OF
DYES
A, W
MFG OF
RUBBER
CHEMICALS
losses
A »W
MFG OF
PHOTOGRAPHIC
CHEMICALS
losses
A,W
FIGURE 22. POSSIBLE ROUTES OF ANILINE INTO THE ENVIRONMENT (1°a)
-------
losses
SCRAP
STORAGE
A,W
A,W
DISPOSAL
losses
MFG OF
DYES
A,W
losses
MFG OF
PESTICIDES
A,W
losses
A ,W
MFG OF \
PHARMACEUTICALS
/ MFG OF \
O-ETHYLANILINE
FIGURE 23. POSSIBLE ROUTES OF O-ETHYLANILINE INTO THE ENVIRONMENT (1°a)
-------
MFG OF
0-DIAMINOBENZENE
SCRAP
STORAGE
DISPOSAL
MFG OF
DYES
PHOTOGRAPHIC
DEVELOPING
AGENT
application
FIGURE 24. POSSIBLE ROUTES OF O-DIAMINOBENZENE INTO THE ENVIRONMENT (1°a)
-------
/ MFG OF
l-DIAMINOBENZEN:
losses
SCRAP
STORAGE
DISPOSAL
A,W
A,W
'A,W
INCINERATOR
losses
MFG OF
DYES
A,W
losses
^MFG OF\
TEXTILES
(DEVELOPING
\agent"l/
TEXTILES
leaching
W,T
DUMPS
open burning
vaporization
FIGURE 25. POSSIBLE ROUTES OF M-DIAMINOBENZENE INTO THE ENVIRONMENT (1°a)
-------
losses
SCRAP
STORAGE
MFG OF \
P-DIAMINOBENZENE'
DISPOSAL
A,W
losses
MFG OF
DYES
A,W
PHOTOGRAPHIC
DEVELOPING
AGENT
application
./MFG OF\.
RUBBER
(ACCELERATOR &
ANTIOXIDANT)
losses
A,W
FIGURE 26. POSSIBLE ROUTES OF P-DIAMINOBENZENE INTO THE ENVIRONMENT (1°a)
-------
SCRAP
STORAGE
MFG OF
DIPHENYLAMINE
A,W
A,T
DISPOSAL
losses
MFG OF
RUBBER
(ANTIOXIDANT
STABILIZER)
A,W
MFG OF
PLASTICS
(STABILIZER)
losses
applicat ion
A,W,T—
-------
losses
SCRAP
STORAGE
-T MFG OF
P-AMINODIPHENYLAMINE
A,W
DISPOSAL
losses
MFG OF
DYES
A,V
losses
losses
A,W
^ MFG OF \
PHOTOGRAPHIC
\CHEMICALS /
MFG OF
PHARMACEUTICALS
FIGURE 28. POSSIBLE ROUTES OF P-AMINODIPHENYLAMINE INTO THE ENVIRONMENT (1°,2°,a)
-------
losses
MFG OF
O-TOLIDINE
SCRAP
STORAGE
A, W
A,W
DISPOSAL
losses
MFG OF
DYES
A,W
CURING AGENT
FOR URETHANE
RESINS
use
FIGURE 29. POSSIBLE ROUTES OF O-TOLIDIIME INTO THE ENVIRONMENT (1°a)
-------
SCRAP
STORAGE
losses
DISPOSAL
A,Wl
MFG
losses
AZO DYES
losses
in use
gasoline
additive
A» T
losses
in use
,A,W,
^ MFG ^
OF
FLOTATION
\ AGENT ^
MFG
of
TOLUIDINES.
FIGURE 30. POSSIBLE ROUTES OF TOLUIDINES INTO THE ENVIRONMENT (1°a)
-------
MFG OF
MELAMINE
losses
SCRAP
STORAGE
DISPOSAL
A,T
OPEN BURNING
VAPORIZATION
3.4x10 tons
v 1972 ^
'A,W
'a,w
losses
DUMPS
losses
application
MFG OF
TEXTILES
(FINISHES)
MFG
COATINGS
TEXTILES
'a,w
INCINERATOR
losses
OPEN BURNING
VAPORIZATION
DUMPS
APPLICATION
MFG
PROTECTIVE
DECORATIVE
LAMINANTS
MFG
WET STRENGTH
PAPER
leaching
INCINERATOR
MELAMINE
RESINS
A,W
'A,W
losses
losses
MFG
MOLDING
COMPOUNDS
MFG
ADHESIVES
FIGURE 31. POSSIBLE ROUTES OF MELAMINE INTO THE ENVIRONMENT (1°a)
-------
losses
SCRAP
STORAGE
A,W
DISPOSAL
losses
MFG OF
DYES
A,W
^ MFG OF \
NAPHTHYLAMINES
FIGURE 32. POSSIBLE ROUTES OF a & 0 - NAPHTHYLAMINE INTO THE ENVIRONMENT (1°pa)
-------
SCRAP
STORAGE
MFG OF
BENZIDINE
DISPOSAL
MFG OF
losses ^ RUBBER
\COMPOUNDING
AGENT
MFG OF
DYES
losses
,W
FIGURE 33. POSSIBLE ROUTES OF BENZIDINE INTO THE ENVIRONMENT (1°a)
------- |